Primary vaccination of infants against hepatitis B can be completed using a combined hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis-Haemophilus influenzae type B vaccine. Immunogenicity and Safety of an Investigational Hexavalent Diphtheria-tetanus-acellular Pertussis-inactivated Poliovirus-hepatitis B-Haemophilus influenzae B Conjugate Combined Vaccine in Healthy 2-, 4-, and 6-month-old Argentinean Infants Avidity maturation of antibody to Haemophilus influenzae type b (Hib) after immunization with diphtheria-tetanus-acellular pertussis-hib-hepatitis B combined vaccine in infants. Immunogenicity and Reactogenicity following Primary Immunisation with a Combined DTaP-HBV Vaccine and a Haemophilus influenzae Type B Vaccine Administered by Separate or Mixed Injection A new combined DTP-HBV-Hib vaccine--strategy for incorporation of Hib vaccination into childhood immunisation programmes. Immunogenicity and reactogenicity of a combined fully liquid DTPw-HepB-Hib pentavalent vaccine in healthy infants: no clinically relevant impact of a birth dose of hepatitis B vaccine. Evidence for induction of polysaccharide specific B-cell-memory in the 1st year of life: plain Haemophilus influenzae type b - PRP (Hib) boosters children primed with a tetanus-conjugate Hib-DTPa-HBV combined vaccine A new DTPw-HB/Hib combination vaccine for primary and booster vaccination of infants in Latin America. Safety and Immunogenicity of a Pentavalent Combination Vaccine (Diphtheria, Tetanus, Acellular Pertussis, Polio and Haemophilus Influenzae Type b Conjugate) When Administered as a Fourth Dose at 15 to 18 Months of Age Four and One-Half-Year Follow-up of the Effectiveness of Diphtheria-Tetanus Toxoids-Acellular Pertussis/Haemophilus influenzae Type b and Diphtheria-Tetanus Toxoids-Acellular Pertussis-Inactivated Poliovirus/H. influenzae Type b Combination Vaccines in Germany Immunogenicity and Reactogenicity of Four Doses of Diphtheria-Tetanus-Three-Component Acellular Pertussis-Hepatitis B-Inactivated Polio Virus-Haemophilus influenzae Type b Vaccine Coadministered with 7-Valent Pneumococcal Conjugate Vaccine Clinical relevance of lower Hib response in DTPa-based combination vaccines. Immunogenicity and reactogenicity of a novel hexavalent DTPa-HBV-IPV/Hib vaccine compared to separate concomitant injections of DTPa-IPV/Hib and HBV vaccines, when administered according to a 3, 5 and 11 month vaccination schedule A combined liquid Hib (PRP-OMPC), hepatitis B, diphtheria, tetanus and whole-cell pertussis vaccine: controlled studies of immunogenicity and reactogenicity. The immunogenicity and reactogenicity of DTPw-HBV/Hib 2.5 combination vaccine: results from four phase III multicenter trials across three continents. Immunogenicity and reactogenicity of two diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus-Haemophilus influenzae type b vaccines administered at 3, 5 and 11–12 months of age Does concomitant injection of a combined diphtheria-tetanus-acellular pertussis - hepatitis B virus - inactivated polio virus vaccine influence the reactogenicity and immunogenicity of commercial Haemophilus influenzae type b conjugate vaccines? REDUCED IMMUNOGENICITY OF DIPHTHERIA AND TETANUS TOXOIDS WHEN COMBINED WITH PERTUSSIS TOXOID Primary vaccination of infants with diphtheria-tetanus-acellular pertussis-hepatitis B virus- inactivated polio virus and Haemophilus influenzae type b vaccines given as either separate or mixed injections. Administration of combined diphtheria and tetanus toxoids and pertussis vaccine, hepatitis B vaccine, and Haemophilus influenzae type b (Hib) vaccine to infants and response to a booster dose of Hib conjugate vaccine. Primary and booster vaccination with DTPw-HB/Hib pentavalent vaccine in Costa Rican children who had received a birth dose of hepatitis B vaccine. Immunogenicity and safety of a new liquid hexavalent combined vaccine compared with separate administration of reference licensed vaccines in infants Immunogenicity and reactogenicity of combined versus separately administered DTPw-HBV and Hib vaccines given to healthy infants at 2, 4 and 6 months of age, with a booster at 18 months. Reactogenicity of DTPa-HBV/Hib vaccine administered as a single injection vs DTPa-HBV and Hib vaccines administered simultaneously at separate sites, to infants at 2, 4 and 6 months of age. Safety and immunogenicity of a combined five-component pertussis-diphtheria-tetanus-inactivated poliomyelitis-Haemophilus B conjugate vaccine administered to infants at two, four and six months of age. Comparative trial to assess the reactogenicity of the diphtheria-tetanus-acellular pertussis (DTPa) vaccine plus Haemophilus influenzae type B (Hib) conjugate vaccine and that of the diphtheria-tetanus-whole cell pertussis (DTPw) vaccine plus Hib conjugate vaccine, administered in single injection a Assessment of the immunogenicity and reactogenicity of a quadrivalent diphtheria, tetanus, acellular pertussis and hepatitis B (DTPa-HBV) vaccine administered in a single injection with Haemophilus influenzae type b conjugate vaccine, to infants at 2, 4 and 6 months of age. Safety and Immunogenicity of a New Fully Liquid DTPw-HepB-Hib Combination Vaccine in Infants Immunogenicity and Safety of an Investigational Fully Liquid Hexavalent Combination Vaccine Versus Licensed Combination Vaccines at 6, 10, and 14 Weeks of Age in Healthy South African Infants DTPw-HB and Hib primary and booster vaccination: combined versus separate administration to Latin American children. Safety and immunogenicity of a hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine at 2, 3, 4, and 12-14 months of age. Safety and immunogenicity of three different formulations of a liquid hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine at 2, 4, 6 and 12-14 months of age. Booster vaccination with hexavalent DTPa-HBV-IPV/Hib vaccine in the second year of life is as safe as concomitant DTPa-IPV/Hib + HBV administered separately. Immunogenicity and safety of Haemophilus influenzae type b conjugate vaccine (HibTITER) and a combination vaccine of diphtheria, tetanus, pertussis and HibTITER (TETRAMUNE) in two-month-old infants. Lot-to-Lot Consistency of a Combined Hexavalent Diptheria-Tentanus-Acellular-Pertussis, Hepatitis B, Inactivated Polio and Haemophilus b Conjugate Vaccine, Adminstered to Healthy Chilean Infants at 2, 4 and 6 Months of Age Evaluation of the immunogenicity and reactogenicity of a DTPa-HBV-IPV combination vaccine Co-administered with a hib conjugate vaccine either as a single injection of a hexavalent combination or as two separate injections at 3, 5 and 11 months of age Safety, reactogenicity and immunogenicity of a combined hexavalent tetanus, diphtheria, acellular pertussis, hepatitis B, inactivated poliovirus vaccine and Haemophilus influenzae type b conjugate vaccine, for primary immunization of infants. Developing optimal search strategies for detecting clinically sound treatment studies in EMBASE. Immunogenicity of a Haemophilus influenzae type b-tetanus toxoid conjugate vaccine when mixed with a diphtheria-tetanus-acellular pertussis-hepatitis B combination vaccine. Immunogenicity and reactogenicity of DTPw–HB/Hib vaccine administered to Colombian infants after a birth dose of hepatitis B vaccine A comparison of immunogenicity and safety of indigenously developed liquid (DTwPHB-Hib) pentavalent combination vaccine (Shan 5) with Easyfive (Liq) and Tritanrix + Hiberix (Lyo) in Indian infants administered according to the EPI schedule Comparison of the immunogenicity and reactogenicity of two commercially available hexavalent vaccines administered as a primary vaccination course at 2, 4 and 6 months of age. Assessment of the compatibility of co-administered 7-valent pneumococcal conjugate, DTaP.IPV/PRP-T Hib and hepatitis B vaccines in infants 2-7 months of age. A new DTPa-HBV-IPV vaccine co-administered with Hib, compared to a commercially available DTPw-IPV/Hib vaccine co-administered with HBV, given at 6, 10 and 14 weeks following HBV at birth. Antibody persistence, PRP-specific immune memory, and booster responses in infants immunised with a combination DTPa-HBV-IPV/Hib vaccine. Comparison of the reactogenicity and immunogenicity of a combined diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polio (DTPa-HBV-IPV) vaccine, mixed with the Haemophilus influenzae type b (Hib) conjugate vaccine and administered as a single injection, with the DTPa-IPV/Hib and he The new DTPw-HBV-Hib combination vaccine can be used at the who schedule with a monovalent dose of hepatitis B vaccine at birth. Feasibility study of the immunogenicity and safety of a novel DTPw/Hib (PRP-T) Brazilian combination compared to a licensed vaccine in healthy children at 2, 4, and 6 months of age. Immunogenicity and safety in infants of a DTwPHib full liquid vaccine Reactogenicity and Immunogenicity Profiles of a Novel Pentavalent Diphtheria-Tetanus–Whole Cell Pertussis–Hepatitis B and Haemophilus Influenzae Type B Vaccine: A Randomized Dose-Ranging Trial of the Hib Tetanus-Conjugate Content
INTRODUCTION Children in Singapore receive vaccination against  hepatitis B virus ( HBV ) at 0 , 1 and 5 or 6 months of age , and vaccination against pertussis , diphtheria , tetanus , and polio at 3 , 4 and 5 months of age . Parents often choose to vaccinate with the combined acellular-pertussis-inactivated polio-Hib vaccine ( DTPa-IPV/Hib ) . We investigated whether a combined hexavalent vaccine , DTPa-HBV-IPV/Hib , could replace the separate administration of DTPa-IPV/Hib and HBV for the final vaccination at 5 months of age ( Trial DTPa-HBV-IPV-075 ) . MATERIAL S AND METHODS In an open study , 150 children were r and omised to complete their vaccination schedule with DTPa-IPV/Hib + HBV or DTPa-HBV-IPV/Hib . RESULTS One month after the final vaccination , there was no difference between groups in seroprotection rates or antibody concentrations against HBV . Seroprotection rates against diphtheria , tetanus , Hib and polio , as well as vaccine response rates to pertussis antigens were also similar between groups . Local and general symptoms occurred at a similar rate after the third dose of either vaccine . CONCLUSION The immunogenicity and reactogenicity of the hexavalent vaccine DTPa-HBV-IPV/Hib ( Infanrix hexa , GSK ) group is comparable to that of separately administered DTPa-IPV/Hib and HBV vaccines . Combined hexavalent vaccine , DTPa-HBV-IPV/Hib , could replace the separate administration of DTPa-IPV/Hib and HBV for vaccination at 5 months of age , thereby reducing the number of injections required Background and Aims : Assessment of a new , fully liquid , investigational hexavalent DTaP-IPV-Hep B-PRP-T vaccine ( Hexaxim , Sanofi Pasteur ) , containing the same active ingredients as Pentaxim ( DTaP-IPV//PRT-T ) and 10 & mgr;g Hansenula polymorpha-derived recombinant hepatitis B ( Hep B ) surface antigen , Sanofi Pasteur , in Argentinean infants . Methods : Infants born to Hep B surface antigen seronegative mothers were r and omized to receive the DTaP-IPV-Hep B-PRP-T vaccine or Pentaxim and Engerix B Pediatrico ( Hep B monovalent ) vaccines at 2 , 4 , 6 months of age . Antibody titers were measured before and 1 month after 3-month primary vaccination . Noninferiority analyses were performed on seroprotection/seroconversion rates . Safety was evaluated descriptively up to 1 month after primary vaccination . Results : A total of 624 participants were enrolled , 312 participants were r and omized to each group , and 604 participants completed the trial . The DTaP-IPV-Hep B-PRP-T vaccine was demonstrated as noninferior to the Pentaxim and Hep B monovalent vaccines with seroprotection/seroconversion rates 1 month postdose 3 for each valence . The anti-Hep B geometric mean titer 1-month postdose 3 for the investigational DTaP-IPV-Hep B-PRP-T primary series was similar to the monovalent Hep B control . The overall incidence of adverse events was similar among the 2 groups . Conclusions : The new , fully liquid , investigational DTaP-IPV-Hep B-PRP-T vaccine ( Hexaxim ) is highly immunogenic and safe when compared with licensed comparators , warranting further development Antibody avidity to Haemophilus influenzae type b ( Hib ) polysaccharide ( PS ) was assessed in infants vaccinated with diphtheria-tetanus-acellular pertussis ( DTaP ) combined with Hib-PS conjugated to tetanus toxoid ( PRP-T ) and hepatitis B ( HB ) ( DTaP-PRP-T-HB )  and after  a PRP-conjugate ( CRM197-OS ) booster 3 - 7 months later . Avidity differed between infants with anti-Hib-PS IgG antibody < 1 or > 1 microg/mL post primary series ( avidity index [ AI ] , 42 % , 95 % confidence interval [ CI ] , 35%-49 % , and 68 % and 63%-72 % , respectively ; P<.0001 ) . For infants with < 1 microgram/mL anti-Hib-PS IgG antibody , mean AI rose by the time of preboost immunization to 61 % ( 95 % CI , 57%-65 % ) , even though total IgG antibody levels fell . Spontaneous Hib-PS antibody rises after primary series DTaP-PRP-T-HB vaccination were followed by high postboost anti-Hib-PS IgG antibody levels and avidity . The DTaP-PRP-T-HB combination vaccine studied elicits high avidity antibody , and affinity maturation appears to occur in the absence of further antigen exposure even in those with very low anti-Hib-PS antibody Abstract Objectives : The aim of this open , r and omised , multicentre trial was to evaluate the immunogenicity and reactogenicity of the tetravalent diphtheria-tetanus-acellular pertussis-hepatitis B ( DTaP-HBV ) vaccine when given either as a mixed or as a separate concomitant injection with the Haemophilus influenzae type b ( Hib ) vaccine  at 3 , 5 and 11 months of age . Methods : Antibody against diphtheria , tetanus , pertussis ( ELISA ) , hepatitis B ( radioimmunoassay ) and Hib polyribosylribitol phosphate ( PRP ) [ radiolabeled antigen binding assay ] was determined . Solicited local and systemic adverse events were evaluated on the day of each vaccination and for three subsequent days . Follow-up of unsolicited and serious adverse events was conducted for 30 days following each vaccination . Results : A total of 360 subjects were enrolled in the study . After completion of the three-dose vaccination course , seroprotective antibody concentrations against diphtheria , tetanus and hepatitis B , together with a pertussis vaccine response , were seen in almost all subjects with immunogenicity results ( n = 336 ) . All subjects had post-vaccination Hib anti-PRP antibody concentrations of at least 0.15 μg/mL , and 97.0 % and 99.4 % , respectively , of the subjects receiving a single or separate injections had Hib anti-PRP antibody concentrations ≥1.0 μg/mL. Addition of the Hib vaccine to the tetravalent DTaP-HBV vaccine did not increase the incidence of local or systemic reactions . Conclusions : Combination of DTaP-HBV and Hib vaccines in a single injection is safe , immunogenic and well tolerated , and thus has the potential to simplify the childhood immunisation schedule in Italy OBJECTIVES To evaluate the immunogenicity and reactogenicity of a pentavalent vaccine prepared by extemporaneously mixing diphtheria-tetanus pertussis-hepatitis B vaccine ( DTP-HBV ) and lyophilised Haemophilus influenzae type B (Hib)-tetanus conjugate vaccines in the same syringe , compared with the same vaccines given as separate , concomitant administrations . DESIGN Open , r and omised comparative study . SETTING Durban , South Africa . SUBJECTS A total of 120 healthy male and female infants were enrolled in the trial and r and omised into two groups ; group 1 received the combined administration ( DTP-HBV-Hib ) , and group 2 received separate administrations of DTP-HBV and Hib vaccines . Vaccines were given as a three-dose primary vaccination course at 2 , 4 and 6 months [ corrected ] of age . OUTCOME MEASURES Antibody levels were measured using st and ard techniques and local and general solicited symptoms were recorded using diary cards . RESULTS All subjects had seroprotective titres against diphtheria and tetanus ; and antipolyribose-ribitol phosphate ( PRP ) titres > or = 0.15 microgram/ml 1 month after the final dose . A vaccine response ( defined as post-vaccination titres > or = 15 ELISA (EL).U/ml in initially seronegative subjects ; and as post-vaccination titres > or = pre-vaccination titres in initially seropositive subjects ) against the pertussis component was seen in 83 % and 85 % of subjects in the groups receiving combined and separate administration . No differences were seen in any of the geometric mean titres ( GMTs ) between the two administrations either 2 months after the second dose or 1 month after the final dose . There was no observed increase in reactogenicity in the group receiving the mixed administration . CONCLUSIONS The results demonstrate that combined DTP-HBV-Hib vaccine is well tolerated and immunogenic OBJECTIVES In this open-label , non-r and omized phase II study , the safety and immunogenicity of a fully liquid diphtheria-tetanus-whole cell pertussis-hepatitis B-Haemophilus influenzae type b ( DTPw-HepB-Hib ) combination vaccine ( Quinvaxem ( ® ) ) were assessed in infants who had or had not received a birth dose of hepatitis B ( HepB ) vaccine . STUDY DESIGN Two groups of infants , ' HepB at birth ' ( n=110 ) and ' no HepB at birth ' ( n=108 ) , were enrolled and received a primary vaccination course using a 2 - 4 - 6 months schedule . RESULTS Seroprotection/seroconversion rates of > 95 % were achieved against all antigens included in the combination vaccine for both study groups . Although significantly higher anti-hepatitis B virus ( p<0.001 ) and anti-tetanus ( p=0.031 ) antibody titers were achieved in group ' HepB at birth ' when compared with group ' no HepB at birth ' , the proportion of ' no HepB at birth ' subjects achieving protective titers was non-inferior to the proportion of subjects in group ' HepB at birth ' . The birth dose of HepB vaccine did not seem to influence the safety pattern of the DTPw-HepB-Hib combination vaccine . CONCLUSIONS The present study demonstrated that the fully liquid DTPw-HepB-Hib vaccine  was safe and immunogenic when administered using a 2 - 4 - 6 months immunization schedule , regardless of whether or not infants had received a dose of HepB vaccine at birth Abstract The lack of an adequate immune response to the major polysaccharide of the Haemophilus influenzae type b ( Hib ) capsule ( polyribosyl ribitol phosphate ) ( PRP ) in very young infants ( < 18 months ) can be overcome by conjugating PRP to a T-cell dependent carrier protein . We studied whether administration of a tetanus-PRP conjugate vaccine reconstituted with a diphtheria-tetanus-acellular pertussis-hepatitis B ( DTPa-HBV ) vaccine as a three dose primary course at 3 , 4 and 5 months of age induced PRP-specific immunological memory , by examining the anti-PRP response to a dose of unconjugated PRP given with the DTPa-HBV booster approximately 1 year later . The unconjugated PRP elicited protective anti-PRP antibody levels ( ≥ 0.15 μg/ml ) in all but 3 of the 369 vaccinees , including 13 infants who failed to demonstrate a measurable immune response after the primary course . In a sub-cohort of 54 subjects all  had anti-PRP levels  ≥ 0.5 μg/ml within 7–14 days of the booster showing a rapid anamnestic type response . Both primary and booster responses were predominantly IgG1 indicating a T-cell dependent response . The DTPa-HBV components elicited protective anti-diphtheria , anti-tetanus and anti-HBs antibody levels in ≥ 98.5 % of vaccinees , and immune responses to each of the acellular pertussis vaccine components in 92.3%–97.3 % of subjects . Conclusion The tetanus-PRP conjugate vaccine not only elicited a good primary humoral response , but also induced immunological memory so that the infants were able to mount a large and rapid immune response to subsequent exposure to plain PRP , indicating that protection against circulating wild-type Hib had been generated . Successful induction of immunological memory occurred even when there was no measurable humoral anti-PRP response to the primary course . Tetanus-PRP conjugate vaccine can be used in combination with DTPa-HBV vaccine , when administered separately or as a single injection in the same syringe , in primary immunisation schedules at 3 , 4 and 5 months of age OBJECTIVES In 1998 the World Health Organization ( WHO ) recommended the inclusion of Haemophilus influenza type B ( Hib ) conjugate vaccines in infant immunization programs , whenever in accordance with national priorities . GlaxoSmithKline Biologicals has developed a new pentavalent combined diphtheria-tetanus-whole cell pertussis-hepatitis B/Hib ( DTPw-HB/Hib ) vaccine containing 5 microg of polyribosylribitol phosphate ( PRP ) , and we assessed the immunogenicity and reactogenicity of primary and booster vaccination of healthy children with this new vaccine compared with a reference regimen consisting of the licensed DTPw-HB ( Tritanrix ) and Hib ( Hiberix ) vaccines given as simultaneous concomitant injections . METHODS We performed a r and omized , double-blind study from September 1998 to August 1999 to establish the immunogenicity and reactogenicity of primary and booster vaccination of healthy children with the new pentavalent combined DTPw-HB/Hib vaccine  given as a single injection , compared with the reference regimen . RESULTS Both vaccination regimens elicited excellent immune responses , with all subjects in both groups achieving seroprotective anti-PRP antibody concentrations of > or = 0.15 microg/mL one month after primary vaccination . The combined DTPw-HB/Hib vaccine was non-inferior to the licensed vaccines in terms of seroprotection/seropositivity/vaccine response rates for all antigen components . Persistence of antibodies against all study vaccine antigens up to the time of booster vaccination was comparable between groups , and a marked increase of all antibody concentrations was observed after the booster dose . Both vaccine regimens were similar in terms of their overall reactogenicity profiles . CONCLUSIONS Our results indicate that the new DTPw-HB/Hib pentavalent combination vaccine provides an efficient and reliable way of implementing WHO recommendations for controlling hepatitis B and Hib infections on a worldwide basis A DTaP-IPV//PRP-T combination vaccine ( Pentacel ™ ) has been universally used in Canada to provide immunization against diphtheria , tetanus , pertussis , polio , and Haemophilus influenzae type b with single injections at 2 , 4 , 6 , and 18 months of age . This r and omized , multicenter study was conducted to evaluate administration of a fourth dose of DTaP-IPV//PRP-T at 15 to 18 months of age , similar to the US immunization schedule . Participants who had received three doses of DTaP-IPV//PRP-T by 8 months of age were enrolled at 12 months and r and omized to receive a fourth dose at 15 , 16 , 17 , or 18 months . Antibody levels for each vaccine antigen were measured prior to and 4 weeks following booster vaccination . Overall , 1782 subjects were immunized and monitored for adverse events , and 735 were evaluated for immune responses .  Pre-immunization antibody levels differed minimally by age , for all antigens . The immune responses elicited by DTaP-IPV//PRP-T were comparable between participants vaccinated at 15 or 16 months and those vaccinated at 17 or 18 months , as demonstrated by specific antibody geometric mean titers , seroprotection/seroresponse rates , and reverse cumulative distribution curves . The fourth dose was well tolerated in all age groups . Toddlers at 15 , 16 , 17 , or 18 months of age are equally suitable recipients for booster immunization with the DTaP-IPV//PRP-T vaccine Background : Recently an increase in the number of invasive Haemophilus influenzae type b ( Hib ) cases was observed in the United Kingdom , which coincided with a temporary change from diphtheria-tetanus toxoids-wild-type pertussis to diphtheria-tetanus toxoids-acellular pertussis ( DTaP ) Hib vaccines . A study in Germany based on approximately 2 years of follow-up , estimated vaccine effectiveness ( VE ) of DTaP/Hib and DTaP-inactivated poliovirus/Hib combination vaccines against invasive Hib disease to be high . Objectives : To assess VE of DTaP-containing Hib vaccines against Hib in Germany with the use of extended follow-up of case surveillance and vaccine uptake . Subjects and Methods : Cases with confirmed systemic Hib infections in children born between June 1 , 1996 and December 31 , 1998 were ascertained by a nationwide active surveillance system from January 1998 through June 2002 . A representative subcohort of 667 children born in the same time frame was r and omly sample d in a nationwide vaccine coverage survey . VE was determined with a case-cohort approach of Cox regression with time-dependent covariates . Results : Thirty-six cases of Hib disease were reported . Of these , 10 were vaccinated with DTaP-containing Hib vaccines only and 20 were not vaccinated . Of the 10 vaccinated cases , 4 had received an incomplete primary series ( 1–2 doses ) , and 6 had received the full primary series ( 3 doses ) , 3 of whom also received the booster dose . VE of combination vaccines against invasive Hib infection was 89.6 % [ 95 % confidence interval ( CI ) , 67.0–96.7 ] for an incomplete primary series , 96.7 % ( 95 % CI 87.7–99.1 ) for a full primary series and 98.5 % ( 95 % CI 94.5–99.6 ) for a booster dose ( irrespective of priming ) . Conclusion : Hib combination vaccines containing acellular pertussis antigens continue to be highly effective in Germany Background : The 7-valent pneumococcal ( 7vPn ) conjugate vaccine is licensed for primary and booster vaccination according to the same immunization schedules as routinely recommended diphtheria-tetanus-pertussis-based childhood vaccines and can be coadministered during the same vaccination visit . Methods : An open , r and omized study evaluated the immunogenicity and safety of a hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus-Haemophilus influenzae type b ( DTPa-HBV-IPV/Hib ) vaccine and a 7vPn conjugate vaccine when coadministered at 2 , 3 and 4 months and 12–23 months of age , compared with the administration of the hexavalent DTPa-HBV-IPV/Hib vaccine given alone . Serum antibody titers were measured before and 1 month after the primary course and before and 1 month after the booster dose . Solicited local and general adverse events were recorded for 4 days and unsolicited adverse events were recorded for 30 days after each vaccine dose . Results : A total of 345 subjects were enrolled for primary vaccination with the hexavalent vaccine  ( 170 without and 175 with the  7vPn vaccine coadministered ) and 266 returned for booster vaccination ( 122 without and 144 with coadministration of the 7vPn vaccine ) . After primary vaccination , antibody responses against the common antigens were similar in both groups , with seroprotection rates of 93.6–100 % and with similar antibody decay before booster vaccination . The fourth dose induced a vigorous booster response , with seroprotection/vaccine response rates of 96.8–100 % . Response to the 7vPn primary and booster vaccination was within previously reported ranges . Differences in reactogenicity result ed from higher incidences of symptoms after concomitant vaccination . Rectal temperature > 39.5 ° C was observed after 1.2 % of the coadministered vaccine doses during primary vaccination and after 2.8 % of the booster vaccine doses . Conclusion : Coadministration of the DTPa-HBV-IPV/Hib and 7vPn vaccines at separate injection sites during the same vaccination visit was effective and safe Combination vaccines are essential to enable administration of all the required antigens in routine infant immunisation schedules at any single visit . Some combinations of diphtheria-tetanus-acellular pertussis ( DTPa ) with Haemophilus influenzae type b ( Hib ) conjugate vaccines have been shown to result in lower Hib titres than when Hib is administered separately . While confirming that a primary series with a DTPa-HBV-IPV/Hib combination gives lower antibody levels than separate Hib conjugates , we show that the nature ( isotype and IgG subclasses ) and function ( avidity and opsonic activity ) of the antibodies are the same , and immunologic memory is induced . It is likely therefore that the DTPa-HBV-IPV/Hib combination will be efficacious against Hib disease Abstract . In an open r and omised trial , 312 eligible infants were enrolled to receive either a single injection of the hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B virus-inactivated polio/Haemophilus influenzae b ( DTPa-HBV-IPV/Hib ) vaccine , or concomitant injections of commercial DTPa-IPV/Hib and HBV vaccines ( comparator ) . Vaccines were administered at 3 , 5 and 11 months of age . The statistical approach for non-inferiority showed that the DTPa-HBV-IPV/Hib vaccine was at least as immunogenic as the comparator vaccines in terms of immunogenicity of all antigens 1 month after the 2nd dose . Non-inferiority criteria were also met immediately before and 1 month after the 3rd dose for all antigens except poliovirus type 3 prior to the 3rd dose . The majority of subjects were seroprotected against diphtheria , tetanus , polyribosyl-ribitol-phosphate , hepatitis B and poliovirus after the 2nd dose and maintained seroprotective antibody levels until the 3rd dose . A marked difference was observed in anti-HBs antibody geometric mean antibody concentrations ( GMCs ) at 1 month after the 2nd dose ( higher GMCs in DTPa-HBV-IPV/Hib group ) . Reactogenicity ( incidence of solicited local and general symptoms ) was similar between the two study groups and no vaccine-related serious adverse events occurred . Conclusion : the new diphtheria-tetanus-acellular pertussis-hepatitis B virus-inactivated polio/Haemophilus influenzae b vaccine administered at 3 , 5 and 11 months of age was safe and at least as immunogenic as the comparator vaccines thus providing an effective and more comfortable option for this infant vaccination schedule We evaluated the immunogenicity and reactogenicity of a new liquid pentavalent combination vaccine , which incorporates a diphtheria , tetanus and whole-cell pertussis vaccine ( DTP ) with Hib ( PRP-OMPC ) and hepatitis B vaccine ( HB ) , in a series of three studies involving 2156 infants . The vaccination schedule was 2 , 4 , 6 and 18 months for all studies . In addition , subjects in the third study also received a dose of monovalent hepatitis B vaccine  at birth . The principal study was a r and omised double blind trial of two separate , but concurrently administered vaccines in each of three groups : pentavalent vaccine [ DTP-Hib-HB ] plus placebo ( Group A , n=619 ) ; quadrivalent vaccine [ DTP-HB ] plus Hib vaccine ( Group B , n=620 ) ; and bivalent vaccine [ Hib-HB ] plus DTP ( Group C , n=226 ) . The second study ( Group D , n=231 ) was an open trial of three separate , but concurrently administered licensed control vaccines ( DTP , Hib and HB ) . The third study ( Group E , n=460 ) administered a dose of monovalent hepatitis B vaccine at birth followed by pentavalent vaccine as for Group A. Subjects were bled prior to the 2- and 18-month vaccinations , and a month after the 6- and 18-month vaccinations . A diary card was used to record subject temperatures and other systemic and local clinical signs for 7 days after each vaccination . The pentavalent vaccine , whether or not preceded by a birth dose of hepatitis B vaccine , was generally well tolerated at all administration times , and had a reactogenicity profile similar to that observed for licensed vaccine controls . Diphtheria and tetanus antibody levels were substantially above protective levels in all study groups . The anti-HBs responses ( % > or = 10 mIU/ml ) following the 6-month dose of vaccines were , respectively , for Groups A-E : 83.2 , 91.7 , 96.5 , 98.8 and 93.9 % , and following the 18-month doses : 87.9 , 97.5 , 98.8 , 98.8 and 92.8 % . Anti-PRP responses ( % > or = 1.0 microg/ml ) following the 6-month dose for Groups A-D were 86.0 , 90.5 , 91.2 , and 74.4 % , and after the 18-month dose for Groups A-E were 97.3 , 98.3 , 98.1 , 97.0 , and 99.5 % . Consistently higher geometric mean titres ( GMTs ) for pertussis antibodies to agglutinogens ( Agg2 , Agg3 ) and pertactin were recorded for the pentavalent vaccine compared to the licensed control vaccine , though they were somewhat lower for pertussigen ( PT ) . Except for the hepatitis B response , antibody responses induced by the pentavalent vaccine to all antigens with a schedule commencing at 2 months of age and completed at 18 months were equivalent to responses to the same antigens induced by the separate , but concurrently administered licensed control vaccines . A regimen of a birth dose of hepatitis B vaccine followed by pentavalent vaccine at 2 , 4 , 6 and 18 months was not countered by any clinical ly significant decrease in seroresponses This paper presents the results of four separate phase III trials , which assessed the immunogenicity and reactogenicity of DTPw-HBV/Hib 2.5 in comparison with licensed Tritanrix-Hep B ( GlaxoSmithKline Biologicals ) and Hiberix ( 10 microg PRP ) , given as separate or mixed injections ( 3 trials ) or with or without hepatitis B vaccine at birth ( 1 trial ) . The immunogenicity of DTPw-HBV/Hib 2.5 was non-inferior to the reference vaccine regimen in terms of seropositivity rates . The overall reactogenicity profile of DTPw-HBV/Hib 2.5 was also similar to that of the reference vaccine regimen . These results confirm the previously established immunogenicity and safety of reduced dose PRP conjugated vaccine regimens The use of combination vaccines in the routine childhood program reduces distress to the recipients and is likely to improve uptake rates and timeliness of vaccination but requires careful evaluation and surveillance . The aim of this study was to evaluate the immunogenicity and reactogenicity of two commercial diphtheria-tetanus- acellular pertussis-hepatitis b-inactivated polio virus-Haemophilus influenzae type b ( DTaP-HBV-IPV/Hib ) combination vaccines when administered to infants at 3 , 5 and 11 - 12 months of age A total of 494 infants were r and omized to receive three doses of either Infanrix hexa ™ ( GlaxoSmithKline Biologicals ; N=246 ) or Hexavac ™ ( Sanofi Pasteur MSD ; N=248 ) in 10 centers in Italy , Finl and and Sweden . After the third dose , antibodies to diphtheria , tetanus , polio and Hib were at the protective level in nearly all infants in both groups whereas the proportion of subjects who had achieved the protective concentration of ≥10 mIU/ml to hepatitis B surface antigen was 99.1 % ( 95 % CI 96.7 - 99.9 ) in the Infanrix hexa ™ group as compared to 94.4 % ( 95 % CI 90.4 - 97.1 ) in the Hexavac ™ group . Antibody titers to all three polio antigens were highest in Italy and lowest in Finl and . Clinical ly relevant general reactions ( such as fever of > 39.5 ° C ) were mostly reported in less than 5 % of the vaccinees . Three doses of DTaP-HBV-IPV/Hib combination vaccines produced sufficient immune responses in nearly all vaccinees Abstract The immunogenic responses and local reactions to four Haemophilus influenzae type b ( Hib ) conjugate vaccines licensed for primary immunisation ( Hiberix , ActHib , Pedvax , HibTITER ) when administered concomitantly but in the opposite thigh with a c and i date diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus vaccine were studied in 549 healthy infants at 3 , 4.5 and 6 months of age .  Local reactions were mild , but different between the four groups , a tetanus conjugate Hib vaccine showing the fewest reactions . All local reactions resolved without sequelae . There was no apparent general reaction . The immunogenic response was similar with all four vaccines , geometric mean concentrations ranging from 4.95 to 7.2 μg/ml . All but one subject had anti-polyribosylribitol phosphate polysaccharide antibody titres ≥0.15 μg/ml , and 88.0 % to 96 % achieved high titres ( > 1.0 μg/ml ) generally associated with long-term protection against Hib disease . Conclusion There does not appear to be any interference with the immune response when current commercial Haemophilus influenzae type b conjugate vaccines are concomitantly administered with a c and i date diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus vaccine as separate injections The effect of pertussis toxoid on the immunogenicity of diphtheria and tetanus toxoids ( DT ) was studied during a double blind efficacy trial of an acellular pertussis vaccine .  Infants received DT with or without pertussis toxoid at 3 , 5 and 12 months of age . Geometric mean concentrations were higher in the DT than in the DT-pertussis toxoid group 1 month ( diphtheria toxoid 4.76 versus 3.58 IU/mL , P = 0.009 ; tetanus toxoid 4.42 versus 2.66 IU/mL , P < 0.0001 ) and 2 years after the third injection ( diphtheria toxoid 0.15 versus 0.10 IU/mL , P < 0.0001 ; tetanus toxoid 0.38 versus 0.18 IU/mL , P < 0.0001 ) . Pertussis toxoid causes a small but significant reduction of the immunogenicity of diphtheria toxoid and tetanus toxoid OBJECTIVE The aim of this open , multicenter , r and omized trial was to evaluate the immunogenicity and reactogenicity of a c and i date combined diphtheria-tetanus-acellular pertussis-hepatitis B virus-inactivated polio virus ( DTaP-HBV-IPV ) vaccine when given as either a mixed or as separate concomitant injections with Haemophilus influenzae type b ( Hib ) vaccine . STUDY DESIGN A total of 359 subjects were r and omized to receive either DTaP-HBV-IPV/Hib ( mixed administration - 180 subjects ) or DTaP-HBV-IPV + Hib ( separate administration in opposite limbs - 179 subjects ) at 2 , 3 , and 4 months of age . RESULTS After vaccination , seroprotective antibody concentrations against diphtheria , tetanus , hepatitis B , and polio viruses and a high ( > or = 97 % ) pertussis vaccine response were seen in almost all study participants . All subjects except one in the mixed administration group had postvaccination Hib anti-PRP antibody concentrations > or = 0.15 microg/mL. Of subjects in the mixed and separate group , 77.2 % ( geometric mean antibody concentration , 2 . 62 microg/mL ) and 88.6 % ( geometric mean antibody concentration , 4.45 microg/mL ) had Hib anti-PRP concentrations > or = 1 microg/mL , respectively . The addition of the Hib component to the 5-component vaccine did not increase the incidence of local or general reactions . CONCLUSION Both administrations of the c and i date vaccine were found to be safe , immunogenic , and well tolerated . Although anti-PRP geometric mean antibody concentrations and the percent of subjects achieving the 1 microg/mL seroprotective level were lower after the mixed administration , they were in the range seen with monovalent Hib vaccines or with other DTaP-based/Hib combinations licensed in some European countries . Therefore both administrations have the potential to simplify childhood immunization We compared antibody levels following separate but simultaneous administration of diphtheria and tetanus toxoids with acellular pertussis vaccine ( DTaP ) containing pertussis toxoid , filamentous hemagglutinin , and pertactin ( PRN ) ; hepatitis B vaccine ; and Haemophilus influenzae type b polysaccharide ( polyribosylribitol phosphate ; PRP ) vaccine conjugated to tetanus toxoid ( PRP-T ) with those following administration of a combination of a DTaP-hepatitis B vaccine-PRP-T to infants at 2 , 4 , and 6 months of age . The antibody response to a booster dose of PRP conjugate vaccine ( CRM197-OS ) in infants with low ( < 1 microgram/mL ) or undetectable ( < 0.10 microgram/mL ) postpriming levels of antibody to PRP was also studied . Antibody levels were quantitated before and after dose 3 by enzyme-linked immunosorbent assay , radioimmunoassay , or neutralization assay . Seroresponse rates were not different between the two vaccine groups except for rates of response to PRP . There was a trend that levels of antibody to all the antigens included in the combination vaccine were lower than those of antibody to antigens in separate vaccines ; for levels of antibody to diphtheria toxoid ( P = .001 ) , PRN ( P < .0001 ) , and PRP ( P < .0001 ) , the differences were significant . Despite low or undetectable postpriming levels of antibody to PRP , high-titered ( geometric mean concentration , 9.02 micrograms/mL ; range , 1.0 - 81.5 micrograms/mL ) , immunoglobulin G-predominant antibody to PRP was produced following a booster dose of CRM197-OS , a finding consistent with a memory response OBJECTIVE The DTPw-HB/Hib pentavalent combination vaccine has been developed following recommendations of the World Health Organization for the introduction of hepatitis B ( HB ) and Haemophilus influenzae type b ( Hib ) vaccines into routine childhood vaccination programs . The objectives of this study were to : 1 ) analyze the immunogenicity and the reactogenicity of the DTPw-HB/Hib pentavalent combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination in a group of children who had received a dose of HB vaccine at birth and 2 ) in the second year of life to assess the antibody persistence as well as the response to a DTPw-HB/Hib or DTPw/Hib booster . METHODS In the first part of the study ( primary -vaccination stage ) , conducted in 1998 - 1999 , we analyzed the immunogenicity and reactogenicity of the DTPw-HB/Hib combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination at 2 , 4 , and 6 months of age in 207 Costa Rican children who had received a dose of HB vaccine at birth . Later , in the booster-vaccination stage of the study , in 1999 - 2000 , in a subset of the children ( 69 toddlers , now 15 - 18 months old ) , antibody persistence was measured , and response to a DTPw-HB/Hib or DTPw/Hib booster was also assessed . RESULTS In both primary -vaccination groups , at least 97.5 % of the infants reached protective levels of antibodies ( seropositivity ) against the antigens employed in the vaccines . The DTPw-HB/Hib pentavalent combination vaccine did not result in more local reactions than did the DTPw-HB vaccine alone , and , in terms of general reactions , there was no clinical ly significant difference between the combination or separate injections , and with the pentavalent vaccine having the benefit of needing one less injection . Nine months after the third dose of the primary -vaccination course , antibody persistence was similar in both groups , with over 93 % of children still having protective/seropositive titers for Hib , HB , and tetanus and about 50 % for diphtheria and Bordetella pertussis . At 15 months of age , virtually all the toddlers responded with a strong boost response to all the vaccine antigens , whether they received the DTPw-HB/Hib pentavalent vaccine or the DTPw/Hib vaccine as a booster . Both booster regimens were equally well tolerated , indicating that up to five doses of the HB vaccine can be given without impact on safety . CONCLUSIONS Our study confirms that the DTPw-HB/Hib pentavalent vaccine is highly immunogenic as a primary vaccination in children who received an HB vaccine at birth , with the pentavalent combination inducing both persisting immunity and boostable memory . The pentavalent vaccine was safe both for primary and booster vaccinations . Thus , this study in Costa Rican infants supports the routine use of the pentavalent DTPw-HB/Hib vaccine as part of childhood vaccination programs in Latin America and the Caribbean Objective . The immunogenicity and safety of a new liquid hexavalent vaccine ( diphtheria-tetanus-acellular pertussis-inactivated polio vaccine-hepatitis B-polyribosyl ribitol phosphate conjugated to tetanus protein ; Hexavac ; Aventis Pasteur MSD , Lyon , France ) are compared with those of reference vaccines [ diphtheria-tetanus-acellular pertussis-inactivated polio vaccine reconstituting lyophilized purified Haemophilus influenzae polysaccharide conjugated to tetanus protein vaccine ( Pentavac ; Aventis Pasteur MSD ) and hepatitis B vaccine ( H-B-Vax II ; Aventis Pasteur MSD ) ] injected separately at the same visit in a prospect i ve multicenter , comparative , open label trial . Methods . Infants were r and omized to receive Hexavac ( n = 423 ) or Pentavac and H-B-Vax II ( n = 425 ) as a primary immunization series at 2 , 4 and 6 months of age .  Seroprotection and seroconversion rates against all antigens at 1 month after the primary series were compared between the two vaccine groups with 95 % confidence intervals ( CI0.95 ) and were considered clinical ly equivalent ( not inferior ) when the upper limit of the 95 % confidence interval on the difference ( reference , hexavalent ) was below predefined differences . Results . Hexavac met and surpassed the predefined criteria for clinical equivalence to Pentavac and H-B-Vax II given concomitantly . It elicited similar seroprotection and seroconversion rates against all antigens . Seroprotection and seroconversion rates obtained 1 month after the third dose of Hexavac were > 90 % for all antigens . The postimmunization antibody geometric mean titers ( GMT ) for hepatitis B and purified Haemophilus influenzae polysaccharide were about 2-fold higher in infants who received the reference vaccines than in infants who had received Hexavac . GMTs for poliovirus antibodies tended to be enhanced in infants vaccinated with Hexavac . GMTs for all other antigens were very similar among both groups . Hexavac was generally well-tolerated . At least one local reaction was reported in 20.3 % of Hexavac injections compared with 15.8 % at the Pentavac injections site and 3.8 % at the H-B-Vax II injections site . These reactions were generally mild and transient . At least one systemic adverse event was reported in 45.7 % of Hexavac injections compared with 42.2 % of Pentavac and H-B-Vax II injections ( mild fever , irritability and drowsiness were most frequently reported ) . The frequency of adverse events was not significantly different between groups . No vaccine-related serious adverse event occurred during the study . Conclusion . This liquid hexavalent vaccine was generally well-tolerated and provided immune responses adequate to be protective against six infectious diseases with a single injection , given at 2 , 4 and 6 months of age OBJECTIVES To determine the immunogenicity and reactogenicity of a combined DTPw-HBV/Hib vaccine , in comparison with DTPw-HBV and Hib vaccines given as separate concomitant injections . METHODS In an open , r and omized study , healthy infants were injected with either DTPw-HBV/Hib vaccine or separate DTPw-HBV and Hib vaccines at 2 , 4 and 6 months of age , with a booster at 18 months . RESULTS Both vaccination regimens were immunogenic , with seropositivity rates of 100 % after the booster vaccination for all vaccine components . Even as early as 2 months after the second dose of the primary vaccination , most patients had seroprotective antibody titers , the proportion of seropositive subjects approaching 100 % for tetanus , hepatitis B , and Hib . Post- primary and post-booster geometric mean titers ( GMTs ) were well above seroprotective thresholds for each vaccine antigen in both groups , with no clinical ly relevant differences in the groups . The separate and combined administrations showed comparable reactogenicity profiles , and neither showed a significant increase in reactogenicity with successive doses . CONCLUSIONS The results of this study support the combination of Hib and DTPw-HBV vaccination in routine infant immunization at 2 , 4 and 6 months of age with a booster at 18 months . Maximum benefit is obtained from compliance with the full course , but substantial benefit is likely to be achieved even in partially compliant patients , provided they receive at least two doses . Furthermore , these results demonstrate the tolerability of a fourth ( booster ) administration , where the addition of the Hib vaccine to DTPw-HBV did not lead to an increase in the overall reactogenicity An open , r and omised , multicentre trial was performed to assess the reactogenicity and safety profile of the administration of a c and i date Haemophilus influenzae type b ( Hib ) conjugate vaccine with a quadrivalent diphtheria-tetanus-acellular pertussis-hepatitis B ( DTPa-HBV ) vaccine as a single injection ( Group 1 ) versus the simultaneous administration of the latter vaccine ( DTPa-HBV ) and an available Hib conjugate vaccine ( Group 2 ) in opposite thighs , as a primary vaccination course to healthy infants at 2 , 4 and 6 months of age . Eight hundred and eighty five infants ( 9.3+/-1.4 weeks old ) were r and omly allocated to Group 1 ( n=665 ) and Group 2 ( n=221 ) .  Oral polio vaccine was given concomitantly to all subjects . Blood sample s ( pre-vaccination and 1 month after the third dose ) were obtained from a subset of infants ( Group 1 , 73 ; Group 2 , 22 ) for serological determinations . Local and general symptoms were recorded by parents on diary cards . 2614 diary cards ( Group 1 , 1966 ; Group 2 , 648 ) were collected . There were no statistically significant differences in the incidence of local and general symptoms between groups . Pain such that the infant cried when limb was moved was reported in 0.6 and 0.2 % in groups 1 and 2 , respectively . Redness and swelling ( > 20 mm in diameter ) were recorded between 2.1 and 3 % in both groups . Fussiness preventing normal activities was the most frequently reported general symptom in both groups ( 1.6 and 1.9 % in groups 1 and 2 , respectively ) . Fever ( rectal temperature > 39.5 degrees C ) was reported in 0.4 % ( Group 1 ) and 0.3 % ( Group 2 ) . All subjects included in the immunogenicity analysis had seroprotective or seropositive titres to the diphtheria , tetanus , hepatitis B and pertussis components of the vaccines . About 99 and 100 % of infants had anti-PRP titres > or = 0.15 mcg/ml in groups 1 and 2 , respectively . This study indicates that DTPa-HBV vaccine given in a single injection with a c and i date Hib conjugate vaccine has a similar reactogenicity profile to that of two commercially available vaccines ( DTPa-HBV , Hib ) given in two simultaneous injections to infants 2 , 4 and 6 months of age Safety , immunogenicity and lot consistency of  five-component pertussis combination vaccine ( CPDT-IPV//PRP-T ) in infants were compared to that of whole cell pertussis combination vaccine ( DPT-IPV//PRP-T ) , as were separate and combined injections of CPDT-IPV and PRP-T. No significant differences in adverse event rates were observed between lots of CPDT-IPV//PRP-T or between separate or combined injections of CPDT-IPV and PRP-T. Minor differences in antibody responses were observed between lots of component pertussis vaccine . Higher concentrations of diphtheria and tetanus antitoxins were induced by separate than by combined injection of CPDT-IPV and PRP-T , but no other differences in immunogenicity were observed . Adverse reactions were more than twice as frequent after whole cell than after component pertussis vaccines . Antibody responses to pertussis toxoid , filamentous hemagglutin and pertactin were significantly greater after component vaccines , while the response to type 3 poliovirus was higher after whole cell vaccine . No significant differences were observed for other vaccine components . CPDT-IPV//PRP-T was safe and immunogenic in infants .  Antibody results were similar to those observed in a Swedish field trial that demonstrated CPDT to be 85 % effective in preventing clinical pertussis BACKGROUND The diphtheria-tetanus-whole-cell pertussis ( DTPw ) vaccine is being replaced in Western countries , and in several Spanish Autonomous Communities , by the diphtheria-tetanus-acellular pertussis ( DTPa ) vaccine . Although the administration of booster doses of DTPw or DTPa and Haemophilus influenzae type b conjugate ( Hib ) vaccines to toddlers is a current practice ina number of countries , there are few data comparing the reactogenicity profiles of their administration as a single injection . SUBJECTS AND METHOD An open , prospect i ve , r and omised , multicentre trial was conducted to compare the reactogenicity profile of a single injection of DTPa and Hib vaccines ( DTPa/Hib ) with that of a single injection of DTPw and Hib vaccines ( DTPw/Hib ) as booster doses to toddlers -- previously primed with DTPw and Hib vaccines .  200 children ( 15.1 + /-1.0 months-old ) were r and omised to receive DTPa/Hib ( group 1;n = 101 ) or DTPw/Hib ( group 2 ; n = 99 ) and followed up to 30 days post-vaccination . All subjects received the oral polio vaccine concomitantly . Local and general symptoms were recorded by parents on diary cards . RESULTS Incidences of any local reaction and any general symptom < < probably related>>/<<suspected>>to vaccination were reported more frequently in group 2 than in group 1 ( p < 0.0001 ) . Pain at the injection site was reported by 29 % and 66 % of subjects in groups 1 and 2 , respectively ( p < 0.0001 ) . Pain such that the child cried when limb was moved was also more frequently recorded in group 2 ( 15 % ) than in group 1 ( 1 % ) ( p < 0.0001 ) . Differences in prevalence of any swelling(16 % in group 1 , 30 % in group 2 ) and swelling > 20 mm reached statistical significance ( p ( 3/4 ) 0.012 ) . Fever ( rectal temperature>= 38 degrees C ) was reported by 17 % and 41 % in groups 1 and 2 subjects , respectively ( p < 0.0001 ) . Fussiness , loss of appetite and restlessness were also more frequently reported in DTPw/Hib subjects and reached statistical significance ( at least p = 0.015).Analgesics/antipyretics were prescribed as a prophylactic treatment in only 14 % of cases ( 9 and 19 subjects in groups 1 and 2 , respectively;p = 0.0424 ) . Antipyretic treatment after vaccination was significantly more prescribed in group 2 ( 27 cases ) than in group 1 ( 8) ( p < 0.015 ) . CONCLUSION The administration of DTPa/Hib as a single injection leads to a better reactogenicity profile than the administration of DTPw/Hib , also as a single injection , as booster doses to toddlers primed with DTPw and Hib vaccines This double-blind , r and omised study was performed to assess the immunogenicity and reactogenicity of three lots of a quadrivalent diphtheria-tetanus-acellular pertussis-hepatitis B vaccine ( DTPa-HBV ) co-administered with three lots of Haemophilus influenzae type b conjugate ( Hib ) vaccine in one injection , as a primary vaccination course in healthy infants at 2 , 4 and 6 months of age . 269 infants ( 8 - 11 weeks of age ) were r and omly allocated to three groups to receive DTPa-HBV/Hib vaccines , concomitantly with oral polio vaccine .  Blood sample s for antibody determinations were taken before vaccination and 1 month after the third dose in 262 subjects . Local and general symptoms were recorded by parents on diary cards . All vaccinees had post-vaccination protective anti-D and anti-T ( > or = 0.1 IU ml-1 ) antibodies , and 98 % had protective anti-HBs antibody titres ( > or = 10 mIU ml-1 ) . There were no statistically significant differences between groups in post-vaccination anti-D , anti-T , anti-HBs antibody geometric mean titres ( GMT ) , these being 3.49 IU ml-1 , 5.92 IU ml-1 and 1109 mIU ml-1 , respectively . All subjects responded to three pertussis components , i.e. pertussis toxin ( PT ) , filamentous haemagglutinin ( FHA ) and pertactin ( PRN ) . Although statistically significant differences in GMTs of anti-PT , anti-FHA and anti-PRN were found between groups , these were not believed to be of any clinical relevance as the minimum GMTs were 60 , 193 and 230 EL.U ml-1 for anti-PT , anti-FHA and anti-PRN , respectively . There were no statistically significant differences in anti-PRP antibody GMT ( 4.05 micrograms ml-1 ) between groups , 100 % and 85 % of subjects having titres > or = 0.15 and 1.0 microgram ml-1 , respectively . No symptoms were reported for one third of the subjects . Fever ( > 38 degrees C ) was reported after 16 % of doses , with < 1 % having > 39.5 degrees C. Almost all local and general symptoms were mild or moderate , and lasted less than 48 h. No subject dropped out due to a severe adverse reaction . The administration of an experimental mix of DTPa-HBV and Hib vaccines in a single injection is safe , well-tolerated and immunogenic for all vaccine components We assessed the safety and immunogenicity of a fully liquid , DTPw-HepB-Hib combination vaccine ( Quinvaxem ™ ) in comparison with separately administered DTPw-Hib and hepatitis B vaccines .  Infants participating in this open-label , r and omized , phase II study received a primary  vaccination  course using a 2 - 3 - 4 month schedule . Blood sample s were taken immediately prior to the first and one month after the third vaccination . Adverse events were assessed over a 7-day post-vaccination period using subject diaries . After completion of the primary vaccination course , 94.7 % [ 95%CI : 89.8 – 97.7 % ] of infants receiving the combination vaccine  achieved protective anti-HBs antibody titers ( ? 10 mIU/mL ) with a mean 39-fold increase in GMTs in comparison with 99.3 % [ 95%CI : 96.3 – 100 % ] seroprotection and a mean 29-fold GMT increase in the comparator group . Diphtheria , tetanus , and Haemophilus influenzae type B ( Hib ) seroprotection rates and pertussis seroconversion rates were also similar between the two groups . There was no statistically significant difference in GMTs for diphtheria between the two groups , but significant differences were shown for tetanus , Hib , and pertussis with higher GMTs for each antigen observed in the comparator group . The combination vaccine was well tolerated , with fever ( body temperature 38 ° C ) being the most frequently reported adverse event in both the DTPw-HepB-Hib ( 12.5 % [ 95%CI : 7.7 – 18.8 % ] ) and comparator ( 12.6 % [ 95%CI : 7.7 – 19.0 % ] ) groups . This study demonstrated that the fully liquid DTPw-HepB-Hib combination vaccine  has safety and immunogenicity profiles similar to the DTPw-Hib and hepatitis B vaccines when administered separately Background : Assessment of primary vaccination of a new fully liquid , hexavalent investigational DTaP-IPV-Hep B-PRP-T vaccine ( Hexaxim ) in South African infants . Methods : Infants were r and omized to the following at 6 , 10 , and 14 weeks of age ( Exp and ed Program on Immunization schedule ) : DTaP-IPV-Hep B-PRP-T ( Group 1 ; N = 286 ) ;  DTwP-Hib , hepatitis B , and OPV vaccines ( Group 2 ; N = 286 ) ; or DTaP-IPV-Hep B-PRP-T vaccine with hepatitis B vaccine at birth ( Group 3 ; N = 143 ) .  Antibody titers were measured before vaccination ( pertussis toxoid , filamentous hemagglutinin ) and post primary vaccination ( all valences ) . Noninferiority analyses were performed for Group 1 versus Group 2 for seroprotection rates . Safety was evaluated from parental reports . Results : Noninferiority ( Group 1 minus Group 2 ) was demonstrated for anti-HBs , -PRP , -diphtheria , -tetanus , and -polio 1 , 2 , 3 ( lower 95 % confidence interval for the difference was −8.20 to 3.46 ) . Anti-HBs antibody titers ≥10 mIU/mL and anti-PRP ≥0.15 & mgr;g/mL were ≥95.4 % in each group . Seroprotection rates were also high for the other antigens . Seroconversion rates ( 4-fold increase from pre- to postvaccination ) were 93.6 % , 83.2 % , and 95.1 % in Groups 1 , 2 , and 3 , respectively , for anti-pertussis toxoid and 93.1 % , 57.7 % , and 90.0 % for anti-filamentous hemagglutinin . Anti-HBs GMTs were 330 , 148 , and 1913 mIU/mL for Groups 1 , 2 , and 3 , respectively . Reactogenicity was similar in each group . Fever ≥39.0 ° C occurred in 1.7 % , 0.4 % , and 0.0 % of infants in Groups 1 , 2 , and 3 , respectively ; no extensive limb swelling , hypotonic-hyporesponsive episodes , or vaccine-related serious adverse events were reported . Conclusions : The new , fully liquid , investigational hexavalent vaccine in the Exp and ed Program on Immunization schedule , with/without hepatitis B at birth , is highly immunogenic and safe compared with control vaccines , warranting further development This multicentre study was design ed to establish the reactogenicity and immunogenicity profiles of primary and booster vaccination with diphtheria , tetanus , and pertussis whole-cell-hepatitis B/Haemophilus influenzae type-b ( DTPw-HB/Hib ) administered as either a syringe mix or as separate injections in 400 Latin American children . Both vaccine regimens were equally well tolerated and elicited post- primary excellent seropositivity rates at or close to 100 % for all five component antigens . With regard to HB , 100 % of subjects in the combined vaccination group , and 98.8 % subjects in the separate injection vaccination group reached seroprotective antibody concentrations ( > or=10 mIU/ml ) 1 month after the primary vaccination course . Equally high anti-PRP antibody concentrations were reached 1 month after vaccination , with 100 % of seroprotected subjects in the combined vaccination group ( antibody concentrations > or=0.15 microg/ml ) , against 99.4 % in the separate injection vaccination group . Seroprotective anti-HBs and anti-PRP antibody concentration levels persisted approximately 1 year after the primary vaccination course , just prior to booster vaccination . Finally , a significant increase of all antibody concentrations could be observed after the booster vaccination , since all but one subject in the separate injection vaccination group had protective levels of anti-HBs and anti-PRP antibodies 1 month after the booster dose . These results suggest that the combination of DTPw-HB and Hib vaccines provides an effective means for increasing vaccine coverage in childhood vaccination programmes Combination vaccines improve parental and provider satisfaction and schedule compliance by decreasing the number of injections . In a Phase 2 , r and omized , double-blind , multicenter study , we compared four formulations of a liquid , hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B virus ( DTaP-IPV-Hib-HBV ) vaccine in 708 infants immunized at 2 , 3 , 4 , and 12 - 14 months of age . The formulations contained identical DTaP and IPV components , differing in the contents of Hib polyribosylribitol phosphate ( PRP ) conjugate component ( tetanus-toxoid [ PRP-T , 12microg ] or Neisseria meningitidis outer-membrane-protein-complex [ PRP-OMPC , 3microg or 6microg ] ) , and in hepatitis B surface antigen ( HBsAg , 10microg or 15microg ) . A minimum acceptable postdose 3 antibody response rate was defined by the lower limit of the 95 % confidence interval exceeding a prespecified target . Rates of adverse events ( AEs ) were similar among groups , with a trend for increased solicited injection-site reactions ( pain , redness , swelling ) with increasing PRP-OMPC and HBsAg concentration . Serious AEs reported by eight subjects were not considered to be vaccine related . All PRP-OMPC formulations met prespecified acceptability criteria for postdose 3 immunogenicity for all antigens : PRP , HBsAg , pertussis , diphtheria , tetanus and polio . Apart from the Hib response , the postdose 3 responses obtained with the PRP-T formulation met the acceptability criterion for each antigen . Postdose 4 responses were acceptable for all antigens in all formulations . All vaccine formulations were well tolerated . The three PRP-OMPC formulations met prespecified immunogenicity criteria , and the one with the lowest PRP-OMPC concentration was selected for further optimization of immunogenicity The current recommended infant vaccination schedules require many injections at multiple sites , which increase stress for infants and parents and may create challenges to vaccination compliance . Therefore , combination vaccines , which reduce the number of injections at each medical visit , can be an essential method to improve compliance . The objective of this study was to assess the safety and immunogenicity of an investigational , liquid , hexavalent , pediatric vaccine at 2 , 4 , 6 , and 12 - 14 months of age . In this multicenter , open-label controlled study , 756 infants were r and omized in approximately equal numbers to receive 0.5mL intramuscular dose of diptheria-tetanus-pertussis-polio-Haemophilus influenzae type b+hepatitis B vaccine , or 1 of 3 double-blind investigational formulations . All formulations included a hepatitis B surface antigen ( HBsAg ) concentration of 10μg/0.5mL. The three hexavalent vaccine formulations used in this study contained either Hib polyribosylribitol phosphate ( PRP ) conjugate component ( tetanus toxoid [ PRP-T , 12μg ] or Neisseria meningitidis outer membrane protein complex [ PRP-OPMC , 3μg or 6μg ] ) : a minimum acceptable postdose 3 antibody response rate for each antigen was defined by the lower limit of a 95 % confidence interval exceeding a prespecified target . Rates of adverse events ( AEs ) were similar among groups , with a trend for increased solicited vaccine-related injection-site reactions ( pain , erythema , swelling ) with increasing PRP-OMPC dose . No serious vaccine-related AEs were reported in the investigational groups . Both PRP-OMPC formulations met prespecified acceptability criteria for all antigens : PRP , HBsAg , pertussis , diphtheria , tetanus and poliovirus . The PRP-T formulation met the acceptability criterion for antibody responses to all antigens other than PRP at postdose 3 . Postdose 4 responses were adequate for all antigens in all formulations . All vaccine formulations were well-tolerated . Both PRP-OMPC formulations met prespecified immunogenicity criteria of PRP-OMPC evaluation The safety and reactogenicity of a booster dose of GSK Biologicals ' hexavalent DTPa-HBV-IPV/Hib vaccine  ( N=4725 ) was compared with the separate administration of  GSK Biologicals ' DTPa-IPV/Hib and HBV vaccines ( N=4474 ) in two open , r and omized multicenter studies ( A and B ) . Solicited symptoms occurring within 4 days of vaccination were recorded on diary cards and serious adverse events ( SAEs ) were collected throughout the study period . In Study A ( N=1149 ) , incidences of solicited symptoms were similar in both groups ; there were no SAEs either reported within 4 days of vaccination or considered to be causally related to vaccination . In study B ( N=8050 ) , where fever was the only solicited symptom , rectal temperature > or = 39.5 degrees C was observed in 2.5 % and 2.8 % of the subjects , respectively . Fever > or = 40.0 degrees C was rare ( 0.6 % ) , and only two cases of febrile convulsions were recorded during the 4 days following vaccination both in the control group . Large swelling reactions ( defined as local injection site swelling with diameter > 50 mm , noticeable diffuse injection site swelling or noticeable increased circumference of the injected limb ) were reported following 2.3 % of the booster vaccine doses , regardless of the vaccine used . Extensive swelling reactions involving an adjacent joint were reported in 0.1 % of the subjects . Two SAEs , both reported after booster doses of DTPa-IPV/Hib and HBV vaccines administered separately , were considered by the investigators to be related to vaccination . Both resolved completely without sequelae . The hexavalent DTPa-HBV-IPV/Hib vaccine and the DTPa-IPV/Hib and HBV vaccines administered separately have similar good reactogenicity and safety profiles when given as booster doses in the second year of life A study was undertaken to evaluate the safety and immunogenicity of a combination vaccine ( TETRAMUNE ) of conjugate Haemophilus influenzae type b ( Hib ) vaccine ( HibTITER ) and DTP ( Diphtheria , Tetanus and Pertussis ) vaccine . A total of 93 healthy children were r and omized to receive either TETRAMUNE  ( combined group ) , or DTP and HibTITER administered concurrently ( separate group ) in separate syringes at approximately 2 , 4 and 6 months of age in Taiwan .  Serologic responses were largely comparable between the two vaccine groups ; almost all subjects were seropositive to Hib PRP ( polyribosylribitol phosphate ) and were protected against diphtheria and tetanus after 2 doses of vaccine and mounted prominent responses to the components of Bordetella pertussis . Subjects in the combined group did not experience more adverse reactions compared with those in the separate group . We concluded that HibTITER was highly immunogenic and safe when administered concurrently with DTP vaccine to Taiwanese children . TETRAMUNE was also safe and immunogenic and might reduce the number of injections to achieve the same protection Objectives : To assess the safety , immunogenicity and lot consistency of a liquid hexavalent combined vaccine ( DTaP-IPV-PRP ~ T-HBs , HEXAVAC ® ) ( Sanofi-Pasteur MSD , France ) administered to infants at 2 , 4 , and 6 months of age . Methods : A total of 1028 infants were vaccinated with one of 3 vaccine lots , in a r and omized , double-blind fashion . Equivalence testing was used to compare post-vaccination seroprotection/seroconversion rates and geometric mean titers ( GMTs ) for each antigen between the three lots . Blood sample s were drawn before vaccination and one month after the third dose . Local and systemic adverse events were monitored for 3 days following each injection . Results : Equivalence between lots was demonstrated for all antigens , on post-dose 3 seroprotection/seroconversion rates and GMTs . Reported rates of local and systemic adverse events tended to increase with subsequent doses . Altogether , 11.8 % of the infants reported at least one adverse local event ( mainly redness and in duration /swelling ) after the first dose and 36.1 % after the third dose . Systemic adverse events ( mainly irritability and fever ) were reported by 39.2 % of the infants after the first dose and by 57.5 % after the third one . Conclusion : Three separate lots of the liquid hexavalent combined vaccine induced consistently protective antibody responses against all antigens . These results and the well established clinical tolerability of this combined vaccine make it suitable for primary immunization of infants at 2 , 4 , and 6 months of age A combined DTPa-HBV-IPV/Hib vaccine containing diphtheria ( D ) , tetanus ( T ) , acellular pertussis ( Pa ) , hepatitis B ( HBV ) and types 1 , 2 and 3 inactivated polioviruses ( IPV ) extemporaneously mixed with a conjugated Haemophilus influenzae type b ( Hib ) vaccine ( Group 1 ) was compared to the DTPa-HBV-IPV and Hib vaccines ( Group 2 ) administered separately at 3 , 5 and 11 months of age ( n=440 ) . A microneutralization assay was used to detect antibodies against the 3 polio virus types ( cut-off 1:8 dil ) , RIA for anti-HBs antibodies ( cut-off 10 mIU/ml ) and ELISA for antibodies against all other vaccine antigens ( cut-off : 0.1 IU/ml for anti-tetanus and anti-diphtheria antibodies ; 5 El . U/ml for antibodies against each of the 3 acellular pertussis antigens and 0.15 μg/ml for anti-PRP antibodies ) . Similar immune responses were observed in both groups 1 month after dose 2 as well as after dose 3 . Six months after dose 2 however , the proportion of subjects maintaining an anti-tetanus antibody concentration ≥0.1 IU/ml was lower in Group 2 and a slight group difference in favour of Group 1 was also observed for anti-PRP , anti-diphtheria and anti-polio type 1 antibody persistence prior to the third dose . The overall incidence of local and general solicited symptoms was similar in both groups . One subject discontinued study vaccination following an SAE considered to be related to vaccination . The DTPa-HBV-IPV/Hib combined vaccine is immunogenic and well tolerated when administered according to a 3 , 5 and 11 month vaccination schedule and can therefore be considered as a feasible alternative to the separate administration of the pentavalent DTPa-HBV-IPV and the monovalent Hib vaccines Safety , reactogenicity and immunogenicity of GSK Biologicals ' hexavalent DTPa-HBV-IPV/Hib vaccine (Infanrix)hexa ) was assessed when used for primary vaccination at 3 , 4 and 5 months of age ( N = 2163 ) , compared to the separate administration of DTPa-IPV/Hib and HBV vaccines ( N = 720 ) . A similar safety and reactogenicity profile was demonstrated for both vaccine regimens , as well as a good immune response for all antigen components . By offering protection against six diseases in a series of single injections , the hexavalent DTPa-HBV-IPV/Hib vaccine was shown to be a safe , well tolerated and immunogenic alternative to primary immunization with licensed separately administered vaccines OBJECTIVE The ability to accurately identify articles about therapy in large bibliographic data bases such as EMBASE is important for research ers and clinicians . Our study aim ed to develop optimal search strategies for detecting sound treatment studies in EMBASE in the year 2000 . METHODS H and search es of journals were compared with retrievals from EMBASE for c and i date search strategies . Six trained research assistants review ed fifty-five journals indexed in EMBASE and rated articles using purpose and quality indicators . C and i date search strategies were developed for identifying treatment articles and then tested , and the retrievals were compared with the h and - search data . The operating characteristics of the strategies were calculated . RESULTS Three thous and eight hundred fifty articles were original studies on treatment , of which 1,256 ( 32.6 % ) were method ologically sound . Combining search terms revealed a top performing strategy ( r and om:.tw . OR clinical trial:.mp . OR exp health care quality ) with sensitivity of 98.9 % and specificity of 72.0 % . Maximizing specificity , a top performing strategy ( double-blind:.mp . OR placebo:.tw . OR blind : .tw . ) achieved a value over 96.0 % , but with compromised sensitivity at 51.7 % . A 3-term strategy achieved the best optimization of sensitivity and specificity ( r and om:.tw . OR placebo:.mp . OR double-blind:.tw . ) , with both these values over 92.0 % . CONCLUSION Search strategies can achieve high performance for retrieving sound treatment studies in EMBASE BACKGROUND Combination vaccines are urgently needed to reduce the number of injections given to young children . The aim of the study was to evaluate the safety and immunogenicity of a combination vaccine that contains diphtheria and tetanus toxoids and acellular pertussis antigens ( DTaP ) , recombinant hepatitis B surface antigen ( HepB ) and Haemophilus influenzae type b ( Hib ) polysaccharide conjugated to tetanus toxoid ( PRP-T ) . METHODS Four hundred five infants were r and omized equally to three groups and immunized at 2 , 4 and 6 months of age with : ( 1 ) DTaP/HepB vaccine used to reconstitute lyophilized PRP-T vaccine and administered as a single injection ; ( 2 ) DTaP/HepB vaccine and PRP-T vaccine administered as two separate injections ; or ( 3 ) DTaP , HepB and PRP-T vaccines administered as three separate injections . Safety was closely monitored , and blood specimens were obtained to assess antibody responses to each vaccine antigen . RESULTS All study vaccines were well-tolerated , and the rates of systemic and injection site reactions were similar between groups . After the third dose the geometric mean antibody concentrations to Hib were significantly lower in subjects in Group 1 ( 1.63 microg/ml ) compared with subjects in Groups 2 and 3 ( 6.26 and 6.15 microg/ml , respectively ; P < 0.0001 ) . Subjects with antibody concentrations < 1.0 microg/ml after the third dose responded well to a booster dose of Hib conjugate vaccine given at 11 to 15 months of age ( 41 of 44 with anti-PRP > or = 1.0 microg/ml ) . Differences between groups for antibody responses to the other vaccine components were not clinical ly significant . CONCLUSIONS Infants given a combined DTaP/ HepB/PRP-T vaccine experienced a significantly lower antibody response to the PRP-T component than infants given PRP-T vaccine as a separate injection . However , the immune response to a booster dose of Hib conjugate vaccine indicated the presence of immunologic memory Objective : To evaluate , in an open study , the immunogenicity , safety and reactogenicity of a birth dose of hepatitis B vaccine followed by a three-dose course of diphtheria – tetanus whole-cell pertussis – hepatitis B vaccine , extemporaneously mixed with Haemophilus influenzae b ( Hib ) vaccine . Methods : At 2 , 4 and 6 months of age , a single group of 120 Colombian infants were enrolled in this study to receive a regimen consisting of three doses of the combination vaccine following a dose of hepatitis B vaccine at birth . Results : Seroprotection/vaccine response rates to all vaccine antigens was 98–100 % 1 month after completion of the full vaccination course . The vaccine had an acceptable reactogenicity profile and the incidence of reported local and general symptoms decreased with the administration of subsequent vaccine doses . Conclusion : The mixed DTPw – HB/Hib vaccine  was safe and well-tolerated , with high immunogenicity against all component antigens . Compared with previous studies , reactogenicity did not increase with the additional dose of hepatitis B vaccine given at birth . The DTPw – HB/Hib combination can be used to provide primary vaccination of infants who have already received a first dose of hepatitis B vaccine at birth The study was planned to assess and compare the immune response and safety of an indigenous DTPwHB-Hib pentavalent liquid combination vaccine ( Shan 5 ) with Easyfive and Tritanrix HB + Hiberix , the two available pentavalent combination vaccines . Four hundred infants were r and omized to receive three doses of either Shan 5 or one of the two comparators . Antibody analysis was performed prior to and four to six weeks post third vaccine dose . Solicited local and systemic events upto three days and unsolicited adverse events in the 30 days follow up period after each dose were recorded . A total of 365 subjects completed the study . Four to six weeks after third dose , 98.32 % of the subjects in Shan 5 group had seroprotective Anti PRP-T IgG antibody concentrations ( ≥0.15 µg/mL ) as compared to 100 % and 98.94 % subjects in Tritanrix HB + Hiberix and Easyfive groups respectively . Seroprotective levels for Anti-HBs ( ≥10 mIU/mL ) were observed in 97.77 % , 97.83 % and 98.94 % subjects in Shan 5 , Tritanrix HB + Hiberix and Easyfive groups respectively . Comparable immune responses were observed for the three other components ( D , T and P ) in all the groups . Four Serious Adverse Events ( SAEs ) were reported ( three with Shan 5 and one with Easyfive ) , all unrelated to the respective vaccines . Most commonly reported adverse events in all the groups were pain at injection site , mild fever ( < 103 ° F ) and minor swelling at injection site . The study proved that Shan 5 was safe and immunogenic compared to the two other licensed vaccines Infants ( N = 459 ) were r and omly assigned to receive either Infanrix hexa or Hexavac vaccines at 2 , 4 and 6 months of age as a primary vaccination schedule . The immunogenicity of the hepatitis B component was statistically significantly higher for Infanrix hexa compared to Hexavac in terms of both seroprotection ( 98.6 % versus 94.7 % , p = 0.0302 ) and GMCs ( 905.6 versus 226.4 , p < 0.0001 ) . Significantly ( p < or = 0.0001 ) higher antibody levels against diphtheria and the 3 polio components were also induced by Infanrix hexa . The responses to tetanus , Hib and pertussis components were similar . The incidences of clinical ly relevant solicited symptoms , unsolicited symptoms or serious adverse events were low in both groups This study assessed compatibility of concurrently administered 7-valent pneumococcal conjugate ( PCV7 ) , hepatitis B ( HB ) and DTaP.IPV/Hib vaccines .  Infants were given DTaP.IPV/Hib and HB at 2 , 4 , 6 months and r and omly assigned ( 2:1 ) to receive PCV7 concurrently or sequentially ( at 3 , 5 , 7 months ) . Antibody levels were compared in 246 concurrent and 122 sequential vaccinees .  Responses to  PCV7 , DTaP.IPV/Hib and HB were generally unaltered with concurrent administration except that Hib responses were increased ( p=0.008 ) and HB responses were reduced ( p=0.006 ) with concurrent dosing , the latter possibly from same thigh injection with DTaP.IPV/Hib . We conclude that PCV7 , DTaP.IPV/Hib and HB are compatible with concurrent , separate injections Three hundred and twenty eligible infants were enrolled in an open r and omized clinical trial and allocated to one of two groups to receive either separate concomitant injections of a c and i date combined DTPa-HBV-IPV and commercial Hib vaccine ( c and i date administration : DTPa-HBV-IPV+Hib ) or separate concomitant injections of licensed DTPw-IPV mixed in the same syringe with Hib and HBV vaccines ( comparator administration : DTPw-IPV/Hib+HBV ) . Vaccines were administered at 6 , 10 and 14 weeks of age preceded by a monovalent dose of HBV at birth . The c and i date vaccine administration was shown to be at least as immunogenic ( primary objective ) as the c and i date administration with respect to the diphtheria , tetanus , polio , HBs and PRP seroprotection rates ( primary endpoints ) . Post vaccination , both vaccine administrations showed an equivalent level of seroprotection with nearly all subjects ( > 96 % ) acquiring seroprotective titers against diphtheria , tetanus , polioviruses , HBsAg and PRP antigens . A markedly higher anti-HBs response post dose 2 at week 14 in the group receiving the c and i date vaccine , 98.6 % of subjects had seroprotective titers ( GMT of 505.7 mIU/ml ) compared with only 88.7 % ( GMT of 107.5 mIU/ml ) in the comparator group . There was a lower incidence of adverse events following the DTPa-based c and i date administration compared with the DTPw-based comparator . Despite the early age and short interval between doses , both administrations were immunogenic , with the concomitant administration of DTPa-HBV-IPV and Hib vaccines showing an improved tolerability over the commercial vaccines DTPw-IPV/Hib and HBV A new single-injection combination vaccine against six diseases has been developed to accommo date the growing number of recommended paediatric vaccines . A pentavalent liquid diphtheria , tetanus , acellular pertussis ( 3-component ) , hepatitis B , and inactivated polio ( types 1 - 3 ) combined vaccine ( DTPa-HBV-IPV ) is extemporaneously mixed with a lyophilized Haemophilus influenza type B ( Hib ) conjugate vaccine ( polyribosyl-ribitol phosphate (PRP)-T ) and given as a single-injection . A cohort of 368 healthy infants was initially studied to evaluate the immunogenicity and reactogenicity of this hexavalent combination given as a primary course at 2 , 4 , and 6 months of age . At 15 months of age , from this cohort , 219 children received a booster dose of a licensed DTPa/Hib ( PRP-T ) vaccine to assess the booster response , while 70 received a challenge dose of unconjugated PRP ( PRP ) vaccine ( to evaluate Hib-specific memory ) plus a separate DTPa vaccine . Seven to 10 days following plain PRP challenge , anti-PRP geometric mean antibody concentrations ( GMCs ) had increased 13-fold to 5.67 microg/ml , and thirty days after conjugated PRP booster vaccination , anti-PRP antibody GMCs increased 102-fold . Both responses are indicative of immune memory . Vaccination was well tolerated following all primary and booster doses , although 10.5 % of booster recipients experienced > 50-mm local swelling at the site of DTPa vaccination . We conclude that DTPa-HBV-IPV/Hib is safe and immunogenic for primary vaccination , and that Hib-specific memory is induced by primary vaccination An open , r and omised , multicentre trial was performed to compare the reactogenicity and safety profile of the administration of a hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio ( DTPa-HBV-IPV ) vaccine administered in one injection mixed with Haemophilus influenzae type b ( Hib ) conjugate vaccine ( Group 1 ) with that of a pentavalent DTPa-IPV vaccine mixed with a Hib vaccine ( DTPa-IPV/Hib ) , simultaneously administered with HBV ( Group 2 ) in two injections in opposite thighs , as a primary vaccination course , to healthy infants at 2 , 4 and 6 months of age . A total of 235 completed the study , 120 from Group 1 and 115 from Group 2 . Blood sample s ( pre-vaccination and 1 month after the third dose ) were obtained from a subset of infants ( Group 1 : 40 ; Group 2 : 31 ) to assess the immune response to vaccination . Local and general solicited symptoms were recorded by parents on diary cards . Seven hundred and five diary cards ( Group 1 : 360 ; Group 2 : 345 ) were collected . The clinical ly relevant and most commonly reported local reaction was pain ( infant cried when the limb was moved ) in 2.5 % ( Group 1 ) and 1.2 % ( Group 2 ) of diary cards . Fever was more frequently reported in Group 1 ( 21 % of diary cards ) than in Group 2 ( 12 % of diary cards ) . However only 3 and 2 % of doses in Groups 1 and 2 , respectively , were responsible for a rectal temperature between 38.6 and 39.5 degrees C and only one case ( Group 2 ) had > or = 39.5 degrees C. Other clinical ly relevant general symptoms were rarely recorded : irritability ( 2 - 2.8 % ) , loss of appetite ( 0.3 - 0.6 % ) and drowsiness ( 0.3 - 0.3 % ) . All subjects included in the immunogenicity analysis had seroprotective titres to diphtheria , tetanus , polio virus types 1 and 3 , Hib . Almost all subjects were seroprotected for anti-polio type 2 and hepatitis B ( with the exception of 1 subject in Group 1 for each antigen ) . The vaccines response rates to pertussis antigens were over 97 and 90 % in Groups 1 and 2 , respectively . This study shows that , from a clinical perspective , the DTPa-HBV-IPV/Hib vaccine given in a single injection has a similar reactogenicity and safety profile to that of two licensed vaccines ( DTPa-IPV/Hib , HBV ) given in two simultaneous injections to infants at 2 , 4 and 6 months of age . This is a valuable advantage , since in some countries , such as Spain and the UK , an additional injection ( for the administration of meningococcal C conjugate vaccine ) has been recently included in the infants ' vaccination calendars An open , r and omized , clinical trial was conducted in order to assess the reactogenicity and immunogenicity of DTPw-HBV and Haemophilus influenzae type b ( Hib ) vaccines when given either as a mixed administration or as separate concomitant injections using the WHO schedule at 6 , 10 and 14 weeks of age , following a dose of HBV at birth . There were no clinical ly relevant differences in the immune response to any component between the mixed and separate administrations . In fact the anti-tetanus GMTs were significantly higher ( p=0.002 ) in mixed administration ( 3.9 IU/ml ) compared with the separate administration ( 1.9 IU/ml ) . However although all subjects achieved anti-PRP titers > or = 0.15 microg/ml , higher anti-PRP GMTs were seen in the group receiving the separate administration . Importantly , the addition of Hib did not adversely alter the reactogenicity profile of DTPw-HBV .  This report which demonstrates that this novel combination can be used in WHO recommended schedule Vaccination of infants with conjugated Haemophilus influenzae type b ( Hib ) vaccines has been proven to reduce Hib meningitis by 95 % and pneumoniae by 20 % . The routine use of Hib vaccine is facilitated by the introduction of combination vaccines into the EPI ( Exp and ed Plan of Immunization ) . The objective of this study was to compare the immunogenicity and reactogenicity of an extemporaneously mixed DTPw/Hib ( diphtheria-tetanus-whole cell pertussis ) combination , using the technology of two Brazilian manufacturers , against a licensed DTPw/Hib European combination in 108 infants vaccinated at 2 , 4 and 6 months according to the local national schedule . The Brazilian combination was highly immunogenic with Hib seroprotection rates ( anti-PRP > 0.15 mg /ml of 98 % after 2 doses and 100 % after 3 ) . Also for tetanus and pertussis the new Brazilian combination was as immunogenic as the European counterpart , except the diphtheria seroprotection rates and titers were lower . There was also no clinical ly relevant difference in reactogenicity . If these feasibility results are confirmed , the Brazilian DTPw/Hib combination should help to boost the uptake of Hib vaccination in Brazil Aim : Combining paediatric vaccines is a rational solution to reduce the number of injections during a single clinical visit , to maintain parents ' compliance and to extend vaccine coverage . Different diphtheria , tetanus and whole cell pertussis (DTwP)‐containing combination vaccines are licensed and used world‐wide . This study assessed the immunogenicity and safety in infants of a combined diphtheria‐tetanus‐whole cell pertussis‐Haemophilus influenzae type b‐CRM197  conjugate full liquid vaccine .  Methods : The safety and efficacy of a combined ready‐to‐use liquid vaccine containing diphtheria and tetanus toxoids , cell suspension of Bordetella pertussis and H. influenzae type b‐CRM197 conjugate vaccine ( DTwPHib ) were assessed in infants eligible for the local Exp and ed Programme on Immunization ( EPI ) in Valencia , Spain . The comparative group received separate injections of reference vaccines DTwP + Hib . Results : Local and systemic reactions and adverse events were generally mild and similar in the two groups . DTwPHib elicited anti‐PRP antibody titres ±0.15 μg ml−1 in 97 % and DTwP + Hib in 94 % of infants . Furthermore , 89 % of DTwPHib and 78 % of DTwP + Hib recipients attained anti‐PRP antibody titres ±1.0 μg ml−1 , signifying long‐term protection . The anti‐PRP geometric mean titre was significantly higher in the combined DTwPHib vaccine group ( 6.65 vs 3.57 μg ml−1 ) . In both groups , 99 % of infants achieved protective ( ±0.01 IU ml−1 ) anti‐diphtheria antibody levels and all children achieved protective ( ±0.1 IU ml−1 ) anti‐tetanus antibody levels . DTwPHib caused a ±2‐fold increase in anti‐pertactin antibody titres in 91 % and a ±4‐fold increase in 82 % of recipients . The corresponding proportions in the DTwP + Hib group were 95 % and 90 % . DTwPHib induced a ±2‐fold increase in anti‐Agg 12 and 3 antibody levels in 79 % and a ±4‐fold increase in 73 % of recipients . The corresponding proportions among DTwP + Hib infants were 85 and 82 % . Conclusion : Overall , the combined liquid vaccine DTwPHib is a safe and effective immunogenic vaccine for EPI use in infants Background : Combined vaccines containing diphtheria-tetanus-pertussis whole-cell ( DTPw ) , Haemophilus influenzae type b ( Hib ) , and hepatitis-B vaccines are essential for the continuing success of vaccination programs in developing nations . This r and omized , dose-ranging study assessed the immunogenicity and reactogenicity of primary and booster vaccination with pentavalent DTPw-HBV/Hib vaccines containing 10 , 5 or 2.5μg of polyribosylribitol phosphate ( PRP ) conjugated to tetanus toxoid ( trials Hib-052/064 ) . Methods : Six hundred eighty infants were r and omized to receive one of 5 vaccine combinations at 6 , 10 , and 14 weeks of age . Of these , 351 received the same  vaccine at 15–24 months of age .  The immune response was evaluated on blood sample s collected 1 month after the 3-dose primary course and before and 6 weeks after the booster dose . Reactogenicity was assessed during a 4-day period after each vaccine dose using diary cards . Results : After primary vaccination , all subjects had seroprotective anti-PRP antibody concentrations ( ≥0.15 μg/mL ) and > 95 % had concentrations ≥1.0 μg/mL , irrespective of the PRP dose administered . Anti-PRP antibody avidity after primary vaccination and antibody persistence until the second year of life were similar among groups . The booster dose induced marked increases in anti-PRP antibody GMCs and antibody avidity , indicative of effective priming and the presence of immune memory . All vaccination regimens elicited good immune responses and comparable antibody persistence to the other vaccine antigens , with significant increases in all antibody concentrations observed after boosting . All vaccination regimens were safe , with similar overall reactogenicity profiles . Conclusion : Hib conjugate vaccines containing reduced amounts of PRP can be effectively combined with the licensed DTPw-HBV vaccine to provide protection against 5 major childhood pathogens in a single injection
BACKGROUND Advantages to combining childhood vaccines include reducing the number of visits , injections and patient discomfort , increasing compliance and optimising prevention .
The World Health Organization ( WHO ) recommends that routine infant immunisation programmes include a vaccination against Haemophilus influenzae ( H. influenzae ) type B ( HIB ) in the combined diphtheria-tetanus-pertussis (DTP)-hepatitis B virus ( HBV ) vaccination .
The effectiveness and safety of the combined vaccine should be carefully and systematic ally assessed to ensure its acceptability by the community .
OBJECTIVES To compare the effectiveness of combined DTP-HBV-HIB vaccines versus combined DTP-HBV and separate HIB vaccinations .