Immunogenicity and Tolerability of a Heptavalent Pneumococcal Conjugate Vaccine Administered at 3, 5 and 12 Months of Age Immunogenicity and impact on nasopharyngeal carriage of a nonavalent pneumococcal conjugate vaccine. Immune response to octavalent diphtheria- and tetanus-conjugated pneumococcal vaccines is serotype- and carrier-specific: the choice for a mixed carrier vaccine 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 Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial Safety and immunogenicity of three doses of an eleven-valent diphtheria toxoid and tetanus protein – conjugated pneumococcal vaccine in Filipino infants Evaluation of the safety and immunogenicity of pneumococcal seven-valent conjugate vaccine (Prevenar) administered in previously unvaccinated Spanish children aged 24 to 36 months. Immunogenicity and reactogenicity of a pneumococcal conjugate vaccine administered combined with a haemophilus influenzae type B conjugate vaccine in United Kingdom infants. A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection. Tolerability and immunogenicity of an 11-valent pneumococcal conjugate vaccine in adults. Efficacy, immunogenicity and safety of heptavalent pneumococcal conjugate vaccine in low birth weight and preterm infants Efficacy and safety of seven-valent conjugate pneumococcal vaccine in American Indian children: group randomised trial Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Northern California Kaiser Permanente Vaccine Study Center Group. Immunogenicity and Safety of the Eleven Valent Pneumococcal Polysaccharide-Protein D Conjugate Vaccine in Infants Efficacy of a pneumococcal conjugate vaccine against acute otitis media. Immunogenicity and safety of a combination pneumococcal-meningococcal vaccine in infants: a randomized controlled trial. Safety and immunogenicity of pneumococcal conjugate vaccine in combination with diphtheria, tetanus toxoid, pertussis and Haemophilus influenzae type b conjugate vaccine The safety, reactogenicity and immunogenicity of a 7-valent pneumococcal conjugate vaccine (7VPnC) concurrently administered with a combination DTaP-IPV-Hib vaccine. Immunogenicity of heptavalent pneumococcal conjugate vaccine in infants. Safety and immunogenicity of three doses of a five-valent pneumococcal conjugate vaccine in children younger than two years with and without human immunodeficiency virus infection.
Background : The recommended vaccination schedule for the pneumococcal conjugate vaccine ( PCV ) includes 4 immunizations , according to the national programs in the United States and some European countries . Other countries use a national schedule for routine vaccinations in early childhood that includes only 3 doses . Aims : The goals were to assess the immunogenicity and tolerability of PCV with a vaccination schedule that included 3 doses during the first 1 year of life ( a 2 + 1 dose schedule ) and to determine the immune responses to concomitantly administered Haemophilus influenzae type b ( Hib ) vaccine . Methods : A total of 101 healthy Swedish infants were enrolled in an open , nonr and omized , multicenter study . PCV was administered concomitantly with ( at separate sites ) a diphtheria-tetanus toxoids-acellular pertussis vaccine , inactivated polio vaccine and Hib conjugate vaccine combination at 3 , 5 and 12 months of age . IgG antibody concentrations for the 7 serotypes included in the PCV and the Hib capsular polysaccharide in serum sample s taken at 3 , 6 , 12 and 13 months were determined with enzyme immunoassays . Local and systemic reactions were monitored for 3 days after each immunization , and serious adverse reactions were monitored for the whole study period . Results : Two doses of PCV induced satisfactory antibody responses , with the exception of serotypes 6B and 23F . The third dose evoked strong responses for all serotypes , which suggests good immunologic priming with the primary series of 2 doses . The mean anti-Hib antibody concentrations were similar to those noted in earlier studies among Swedish children . The PCV was well tolerated . Conclusion : The pneumococcal antibody concentrations at 13 months were comparable with those noted previously with the 4-dose schedule . The results suggest that the implementation of a 2 + 1 dose schedule for PCV should be considered The safety , immunogenicity , and impact on carriage of a nonvalent pneumococcal vaccine given at ages 6 , 10 , and 14 weeks were examined in a double-blind , r and omized , placebo-controlled trial in 500 infants in Soweto , South Africa . No serious local or systemic side effects were recorded . Significant antibody responses to all pneumococcal serotypes were observed 4 weeks after the third dose . Haemophilus influenzae type b polyribosylribitol phosphate ( geometric mean titer , 11.62 microg/mL ) and diphtheria ( 1.39 IU/mL ) antibodies were significantly higher in children receiving pneumococcal conjugate , compared with placebo recipients ( 4.58 microgram/mL and 0.98 IU/mL , respectively ) . Nasopharyngeal carriage of vaccine serotypes decreased in vaccinees at age 9 months ( 18 % vs. 36 % ) , whereas carriage of nonvaccine serotypes increased ( 36 % vs. 25 % ) . Carriage of penicillin-resistant pneumococci ( 21 % vs. 41 % ) and cotrimoxazole-resistant pneumococci ( 23 % vs. 35 % ) were significantly reduced 9 months after vaccination , compared with controls Background . Development of protein-conjugated pneumococcal vaccines for infants has led to formulations that are immunogenic in the age group at highest risk for pneumococcal diseases . This study focuses on the search for an optimal formulation . Methods . In a r and omized trial Icel and ic infants ( n = 160 ) were immunized at age 3 , 4 and 6 months with one of two octavalent pneumococcal conjugate vaccines ( serotypes 3 , 4 , 6B , 9V , 14 , 18C , 19F and 23F conjugated to diphtheria toxoid ( PncD ) or tetanus protein ( PncT ) followed with a booster of either the same conjugate or 23-valent polysaccharide vaccine at 13 months . Safety data were collected after each vaccination , and IgG responses ( enzyme-linked immunosorbent assay ) were measured at 3 , 4 , 6 , 7 , 13 and 14 months . Results . Both conjugates were safe and caused fewer local reactions than the routine vaccines ( P < 0.0001 ) . At 7 months both groups had significant IgG response to all serotypes . The geometric mean concentration range was 0.35 to 4.09 and 0.65 to 3.38 & mgr;g/ml for PncD and PncT , respectively , with 88.2 to 100 % and 92.4 to 100 % of subjects reaching ≥0.15 & mgr;g/ml . The PncD gave better primary responses to serotypes 3 , 9V and 18C , whereas PncT gave better response to serotype 4 . Similar responses were induced to the other serotypes . Good booster IgG responses were obtained in all vaccine groups ; 97.5 to 100 % of subjects reached ≥1 & mgr;g/ml . Conclusions . Both octavalent pneumococcal conjugates were safe and immunogenic in infants . Based on the results from this and similar trials , a mixed diphtheria and tetanus pneumococcal conjugate vaccine was design ed to provide the optimal immune response to each serotype 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 BACKGROUND Pneumonia is estimated to cause 2 million deaths every year in children . Streptococcus pneumoniae is the most important cause of severe pneumonia . We aim ed to assess the efficacy of a nine-valent pneumococcal conjugate vaccine in children . METHODS We undertook a r and omised , placebo-controlled , double-blind trial in eastern Gambia . Children age 6 - 51 weeks were r and omly allocated three doses of either pneumococcal conjugate vaccine ( n=8718 ) or placebo ( 8719 ) , with intervals of at least 25 days between doses . Our primary outcome was first episode of radiological pneumonia . Secondary endpoints were clinical or severe clinical pneumonia , invasive pneumococcal disease , and all-cause admissions . Analyses were per protocol and intention to treat . FINDINGS 529 children assigned vaccine and 568 allocated  placebo were not included in the per- protocol analysis . Results of per- protocol and intention-to-treat analyses were similar . By per- protocol analysis , 333 of 8189 children given vaccine had an episode of radiological pneumonia compared with 513 of 8151 who received placebo . Pneumococcal vaccine efficacy was 37 % ( 95 % CI 27 - 45 ) against first episode of radiological pneumonia . First episodes of clinical pneumonia were reduced overall by 7 % ( 95 % CI 1 - 12 ) . Efficacy of the conjugate vaccine was 77 % ( 51 - 90 ) against invasive pneumococcal disease caused by vaccine serotypes , 50 % ( 21 - 69 ) against disease caused by all serotypes , and 15 % ( 7 - 21 ) against all-cause admissions . We also found an efficacy of 16 % ( 3 - 28 ) against mortality . 110 serious adverse events arose in children given the pneumococcal vaccine compared with 131 in those who received placebo . INTERPRETATION In this rural African setting , pneumococcal conjugate vaccine has high efficacy against radiological pneumonia and invasive pneumococcal disease , and can substantially reduce admissions and improve child survival . Pneumococcal conjugate vaccines should be made available to African infants Background An 11-valent pneumococcal conjugate vaccine could provide significantly larger reduction in pneumococcal disease burden than the currently available 7-valent vaccine formulation in many countries . Methods In total , 50 infants were enrolled to this open , uncontrolled study , which evaluated the safety and immunogenicity of an aluminium adjuvanted 11-valent mixed-carrier diphtheria toxoid or tetanus protein-conjugated vaccine ( 11-PncTD ) when administered in three doses at 6 , 10 and 14 weeks of age simultaneously with DTwP//PRP-T and OPV vaccines in Filipino infants . Results The rates of local reactions between the two injection sites , those associated with the 11-PncTD vaccine and those with the DTwP//PRP-T were almost of equal frequency for all three vaccine doses except for in duration , which was significantly more common in the DTP//PRP-T injection site . Fever was present in 39 % , 22 % and 21 % of infants following each of the three doses . Antibody responses were determined by an enzyme immunoassay method before the first vaccination and after the three doses . The vaccine elicited a significant anti-pneumococcal polysaccharide antibody response against all serotypes included in the vaccine , except for type 14 , for which the pre-vaccination geometric mean antibody concentration ( GMC ) was high ( 1.61 μg/ml ) . The GMCs one month after the vaccination series ranged from 1.1 micrograms/ml for type 6B to 23.4 μg/ml for type 4 . Conclusion The 11-PncTD vaccine is safe , well-tolerated and immunogenic . The effectiveness of the non-adjuvanted formulation of the vaccine in preventing pneumonia is currently being evaluated in the Philippines UNLABELLED This study evaluates the safety and immunogenicity of pneumococcal seven-valent conjugate vaccine ( Prevenar ) in 115 children , aged 2 - 3 years ( 24 - 36 months ) , who have not been previously vaccinated with Prevenar .  RESULTS SAFETY As for local reactions , 40 % of children reported erythema , 32.2 % in duration and 39.1 % tenderness at the injection site . Regarding systemic reactions , fever > or 38 C was recorded in 7 % of patients . Other commonly reported events were decreased appetite ( 24.3 % ) , restlessness ( 20 % ) , and fussiness ( 18.3 % ) . IMMUNOGENICITY After vaccination , more than 98 % of the subjects achieved antibody levels of > or = 0.15 microg/mL for all seven serotypes and more than 95 % achieved antibody levels > or = 0.50 microg/mL for all serotypes . CONCLUSIONS Pneumococcal seven-valent conjugate vaccine ( Prevenar ) was safe , well tolerated and highly immunogenic when administered in previously unvaccinated children aged 14 - 36 months BACKGROUND Streptococcus pneumoniae is a major disease burden in young children and the incidence of antibiotic-resistant pneumococcal strains is increasing . Multivalent pneumococcal saccharide-protein conjugate vaccines have recently been developed . OBJECTIVES To assess the immunogenicity and reactogenicity of a 7-valent pneumococcal conjugate vaccine ( 7VPnC ) administered as a separate injection or as a combined injection with Haemophilus influenzae type b vaccine ( HbOC ) at 2 , 3 and 4 months of age . METHODS R and omized controlled trial of 368 healthy UK infants receiving routine vaccines only ( control group ) , routine vaccines and 7VPnC as a separate injection ( separate group ) , or routine vaccines and 7VPnC combined with HbOC ( combined group ) at 2 , 3 and 4 months . The control group received 7VPnC at 5 , 6 and 7 months . All groups received pneumococcal polysaccharide vaccine at 13 to 16 months . Anticapsular IgG antibodies to 7VPnC serotypes were measured at 2 , 5 , 13 and 14 months and safety data collected . RESULTS IgG antibody concentrations at 5 months were higher in the two treatment groups compared with the controls for all 7VPnC serotypes ( P < 0.001 ) and higher in the separate group than the combined group for five 7VPnC serotypes ( P < 0.05 ) . For both treatment groups antibody concentrations were higher at 14 months ( range , 6.6 to 25.3 microg/ml ) than at 5 months ( range , 0.6 to 2.5 microg/ml ) for all 7VPnC serotypes ( P < 0.001 ) . CONCLUSION 7VPnC was well-tolerated , safe and immunogenic when administered as a separate or as a combined 7VPnC/HbOC injection . Although antibody responses were lower in the infants who received the combination compared with those who received 7VPnC as a separate injection , marked anamnestic responses to polysaccharide challenge were observed , suggesting that both groups were immunologically primed BACKGROUND Acute respiratory tract infections caused by Streptococcus pneumoniae are a leading cause of morbidity and mortality in young children . We evaluated the efficacy of a 9-valent pneumococcal conjugate vaccine in a r and omized , double-blind study in Soweto , South Africa . METHODS At 6 , 10 , and 14 weeks of age , 19,922 children received the  9-valent pneumococcal polysaccharide vaccine conjugated to a noncatalytic cross-reacting mutant of diphtheria toxin ( CRM197 ) , and 19,914 received placebo .  All children received Haemophilus influenzae type b conjugate vaccine .  Efficacy and safety were analyzed according to the intention-to-treat principle . RESULTS Among children without human immunodeficiency virus ( HIV ) infection , the vaccine reduced the incidence of a first episode of invasive pneumococcal disease due to serotypes included in the vaccine by 83 percent ( 95 percent confidence interval , 39 to 97 ; 17 cases among controls and 3 among vaccine recipients ) . Among HIV-infected children , the efficacy was 65 percent ( 95 percent confidence interval , 24 to 86 ; 26 and 9 cases , respectively ) . Among children without HIV infection , the vaccine reduced the incidence of first episodes of radiologically confirmed alveolar consolidation by 20 percent ( 95 percent confidence interval , 2 to 35 ; 212 cases in the control group and 169 in the vaccinated group ) in the intention-to-treat analysis and by 25 percent ( 95 percent confidence interval , 4 to 41 ; 158 and 119 cases , respectively ) in the per- protocol analysis ( i.e. , among fully vaccinated children ) . The incidence of invasive pneumococcal disease caused by penicillin-resistant strains was reduced by 67 percent ( 95 percent confidence interval , 19 to 88 ; 21 cases in the control group and 7 in the vaccinated group ) , and that caused by strains resistant to trimethoprim-sulfamethoxazole was reduced by 56 percent ( 95 percent confidence interval , 16 to 78 ; 32 and 14 cases , respectively ) . CONCLUSIONS Vaccination with a 9-valent pneumococcal conjugate vaccine reduced the incidence of radiologically confirmed pneumonia . The vaccine also reduced the incidence of vaccine-serotype and antibiotic-resistant invasive pneumococcal disease among children with and those without HIV infection We studied the safety and immunogenicity in healthy adults of an 11-valent pneumococcal conjugate vaccine . Capsular polysaccharides ( PS ) of serotypes 1 , 4 , 5 , 7F , 9V , 19F and 23F were conjugated to tetanus toxoid , and of serotypes 3 , 6B , 14 and 18C to diphtheria toxoid .  Ten subjects received the conjugate vaccine with and the other ten subjects  without aluminium hydroxide adjuvant . The reference vaccine was a marketed 23-valent PS vaccine .  Safety data were recorded over 5 days after the immunisation . IgG antibody concentrations , avidity and subclass distribution were measured by EIA . The conjugate without aluminium induced more local adverse effects than the conjugate with aluminium or PS vaccine . All vaccines evoked significant antibody increases to all vaccine specific antigens . Both conjugate vaccines induced antibodies mainly of IgG(2 ) subclass , and adjuvanted conjugate vaccine induced IgG antibodies with increased avidity . This first administration , to man , of a mixed protein carrier 11-valent pneumococcal conjugate vaccine demonstrated its ability to induce an immune response without significant adverse effects , enabling further study on its use in paediatric population Objective . To determine the efficacy , immunogenicity and safety of the heptavalent CRM197 pneumococcal conjugate vaccine ( PCV ) in low birth weight ( LBW ) and preterm ( PT ) infants against invasive pneumococcal disease caused by vaccine types . Methods . In a r and omized double blind trial of 37 868 infants given either PCV or meningococcal type C conjugate vaccine ( MCV ) , 1756 infants < 750 g < 2500 g ( LBW ) and 4340 infants from 32 to < 38 weeks old ( PT ) were identified . Risk of invasive pneumococcal disease in LBW and PT infants was compared with risk in normal birth weight ( NBW ) and full term ( FT ) infants . Local and systemic events observed within 48 h of recent vaccine were assessed by telephone interviews and similar comparisons made . Premature infant Emergency Department visits and hospitalization were also identified and compared with FT and NBW infants . Results . Initiation of immunization and intervals between doses were similar for all groups . The risk ratio for invasive pneumococcal diseases for LBW infants compared with NBW infants was 2.6 ( P = 0.03 ) , and for PT compared with FT infants the risk ratio was 1.6 ( P = 0.06 ) . Vaccine efficacy for both groups was 100 % . PCV was as immunogenic in LBW and PT as in NBW and FT infants . Fever and local events after PCV vaccination were similar when adjusted for clustering among multiple doses per child . When stratified for individual doses there was more redness and swelling for LBW infants and more swelling for PT infants after Dose 3 . Isolated local and systemic reactions were more commonly seen with PCV than with MCV , a pattern similar to that in NBW and FT infants . Hospitalization rates were similar for PCV and MCV recipients . Conclusion . These data support the use of PCV in LBW infants and PT infants BACKGROUND Streptococcus pneumoniae is the main cause of invasive bacterial disease in children aged younger than 2 years . Navajo and White Mountain Apache children have some of the highest rates of invasive pneumococcal disease documented in the world . We aim ed to assess the safety and efficacy of a seven-valent polysaccharide protein conjugate pneumococcal vaccine ( PnCRM7 ) against such disease . METHODS In a group-r and omised study , we gave this vaccine to children younger than 2 years from the Navajo and White Mountain Apache Indian reservations ; meningococcal type C conjugate vaccine ( MnCC ) served as the control vaccine . Vaccine schedules were determined by age at enrollment . We recorded episodes of invasive pneumococcal disease and serotyped isolates . Analyses were by intention to treat and per protocol . FINDINGS 8292 children enrolled in the trial . In the per protocol analysis of the primary efficacy group ( children enrolled by 7 months of age ) there were eight cases of vaccine serotype disease in the controls and two in the PnCRM7 group ; in the intention-to-treat analysis we noted 11 cases of vaccine serotype disease in the MnCC control group and two in the PnCRM7 group . After group r and omisation had been controlled for , the per protocol primary efficacy of PnCRM7 was 76.8 % ( 95 % CI -9.4 % to 95.1 % ) and the intention-to-treat total primary efficacy was 82.6 % ( 21.4 % to 96.1 % ) . INTERPRETATION PnCRM7 vaccine prevents vaccine serotype invasive pneumococcal disease even in a high risk population . Other regions with similar disease burden should consider including this vaccine in the routine childhood vaccine schedule OBJECTIVE To determine the efficacy , safety and immunogenicity of the heptavalent CRM197 pneumococcal conjugate vaccine against invasive disease caused by vaccine serotypes and to determine the effectiveness of this vaccine against clinical episodes of otitis media . METHODS The Wyeth Lederle Heptavalent CRM197 ( PCV ) was given to infants at 2 , 4 , 6 and 12 to 15 months of age in a double blind trial ; 37,868 children were r and omly assigned 1:1 to receive either the pneumococcal conjugate vaccine or meningococcus type C CRM197 conjugate . The primary study outcome was invasive disease caused by vaccine serotype . Other outcomes included overall impact on invasive disease regardless of serotype , effectiveness against clinical otitis media visits and episodes , impact against frequent and severe otitis media and ventilatory tube placement . In addition the serotype-specific efficacy against otitis media was estimated in an analysis of spontaneously draining ears . RESULTS In the interim analysis in August , 1998 , 17 of the 17 cases of invasive disease caused by vaccine serotype in fully vaccinated children and 5 of 5 of partially vaccinated cases occurred in the control group for a vaccine efficacy of 100 % . Blinded case ascertainment was continued until April , 1999 . As of that time 40 fully vaccinated cases of invasive disease caused by vaccine serotype had been identified , all but 1 in controls for an efficacy of 97.4 % ( 95 % confidence interval , 82.7 to 99.9 % ) , and 52 cases , all but 3 in controls in the intent-to-treat analysis for an efficacy of 93.9 % ( 95 % confidence interval , 79.6 to 98.5 % ) . There was no evidence of any increase of disease caused by nonvaccine serotypes . Efficacy for otitis media against visits , episodes , frequent otitis and ventilatory tube placement was 8.9 , 7.0 , 9.3 and 20.1 % with P < 0.04 for all . In the analysis of spontaneously draining ears , serotype-specific effectiveness was 66.7 % . CONCLUSION This heptavalent pneumococcal conjugate appears to be highly effective in preventing invasive disease in young children and to have a significant impact on otitis media Background : Development is ongoing to increase the serotype coverage of pneumococcal conjugate vaccines . We report here the immunogenicity and safety of a new 11-valent pneumococcal conjugate vaccine ( Pn-PD ) in infants . Methods : In a r and omized , single blind study , 154 Finnish infants received 1 of 3 regimens : 4 doses of Pn-PD at 2 , 4 , 6 and 12–15 months ; 3 doses of the Pn-PD at 2 , 4 and 6 months and 1 dose of 23-valent polysaccharide vaccine ( PncPS ) at 12–15 months ; or 3 doses of the hepatitis B vaccine at 2 , 4 and 6 months and Pn-PD at 12–15 months . Serum IgG antibodies to vaccine serotypes 1 , 3 , 4 , 5 , 6B , 7F , 9V , 14 , 18C , 19F and 23F were measured with an enzyme immunoassay at the ages of 2 , 7 and 12–15 months and at 4 or 28 days after the last vaccination . Local and systemic reactions were recorded by parents during 8 days after each dose . Serious adverse reactions were recorded during the entire study period . Results : There was a significant increase in the IgG concentrations to vaccine serotypes after 3 doses of Pn-PD . Antibody concentrations after the primary series varied between 1.26 and 4.92 & mgr;g/ml depending on the serotype and study group . PncPS vaccine induced a better booster response than the Pn-PD , measured at 28 days after the fourth dose . IgG concentrations after the Pn-PD booster ranged between 1.60 and 9.63 & mgr;g/ml and after the PncPS booster between 4.24 and 40.54 & mgr;g/ml , depending on the serotype . The antibody concentrations after the first dose of Pn-PD administered at 12–15 months increased significantly but were lower than after the fourth dose at the same age . No significant antibody increase was measured 4 days after the vaccinations at 12–15 months . The safety profile of the vaccine was acceptable . Conclusions : The Pn-PD we tested was immunogenic and safe in infants BACKGROUND Ear infections are a common cause of illness during the first two years of life . New conjugate vaccines may be able to prevent a substantial portion of cases of acute otitis media caused by Streptococcus pneumoniae . METHODS We enrolled 1662 infants in a r and omized , double-blind efficacy trial of a heptavalent pneumococcal polysaccharide conjugate vaccine in which the carrier protein is the nontoxic diphtheria-toxin analogue CRM197 . The children received either the study vaccine or a hepatitis B vaccine as a control at 2 , 4 , 6 , and 12 months of age . The clinical diagnosis of acute otitis media was based on predefined criteria , and the bacteriologic diagnosis was based on a culture of middle-ear fluid obtained by myringotomy . RESULTS Of the children who were enrolled , 95.1 percent completed the trial . With the pneumococcal vaccine , there were more local reactions than with the hepatitis B vaccine but fewer than with the combined whole-cell diphtheria-tetanus-pertussis and Haemophilus influenzae type b vaccine that was administered simultaneously . There were 2596 episodes of acute otitis media during the follow-up period between 6.5 and 24 months of age . The vaccine reduced the number of episodes of acute otitis media from any cause by 6 percent ( 95 percent confidence interval , -4 to 16 percent [ the negative number indicates a possible increase in the number of episodes ] ) , culture-confirmed pneumococcal episodes by 34 percent ( 95 percent confidence interval , 21 to 45 percent ) , and the number of episodes due to the serotypes contained in the vaccine by 57 percent ( 95 percent confidence interval , 44 to 67 percent ) . The number of episodes attributed to serotypes that are cross-reactive with those in the vaccine was reduced by 51 percent , whereas the number of episodes due to all other serotypes increased by 33 percent . CONCLUSIONS The heptavalent pneumococcal polysaccharide-CRM197 conjugate vaccine is safe and efficacious in the prevention of acute otitis media caused by the serotypes included in the vaccine CONTEXT The success of conjugate vaccines in decreasing invasive disease due to Streptococcus pneumoniae and group C Neisseria meningitidis has placed pressure on crowded infant immunization schedules , making development of combination vaccines a priority . OBJECTIVE To determine the safety and immunogenicity of a combination 9-valent pneumococcal-group C meningococcal conjugate c and i date vaccine ( Pnc9-MenC ) administered as part of the routine UK infant immunization schedule at ages 2 , 3 , and 4 months . DESIGN , SETTING , AND PARTICIPANTS Phase 2 r and omized controlled trial conducted from August 2000 to January 2002 and enrolling 240 healthy infants aged 7 to 11 weeks from 2 UK centers , with home follow-up visits at ages 2 , 3 , 4 , and 5 months . INTERVENTION Pnc9-MenC ( n = 120 ) or monovalent group C meningococcal conjugate vaccine ( MenC ) ( n = 120 ) administered in addition to routine immunizations ( diphtheria and tetanus toxoids and whole-cell pertussis [ DTwP ] , Haemophilus influenzae type b [ Hib ] polyribosylribitol phosphate-tetanus toxoid protein conjugate , oral polio vaccine ) . MAIN OUTCOME MEASURES Group C meningococcal immunogenicity measured by serum bactericidal titer ( SBT ) 1 month following the third dose ; rates of postimmunization reactions . RESULTS MenC component immunogenicity was reduced in the Pnc9-MenC vs the MenC group ( geometric mean SBT , 179 [ 95 % confidence interval { CI } , 133 - 243 ] vs 808 [ 95 % CI , 630 - 1037 ] , respectively ; P<.001 ) . The proportion with group C meningococcal SBT greater than 1:8 was lower in the Pnc9-MenC vs the MenC group ( 95 % vs 100 % , P = .05 ) . The geometric mean concentration of antibodies to concomitantly administered Hib vaccine was reduced in the Pnc9-MenC vs the MenC group ( 2.11 [ 95 % CI , 1.57 - 2.84 ] microg/mL vs 3.36 [ 95 % CI , 2.57 - 4.39 ] microg/mL ; P = .02 ) , as were antibodies against diphtheria ( 0.74 [ 95 % CI , 0.63 - 0.87 ] microg/mL vs 1.47 [ 95 % CI , 1.28 - 1.69 ] microg/mL ; P<.001 ) . Pnc9-MenC was immunogenic for each of 9 contained pneumococcal serotypes , with responses greater than 0.35 microg/mL observed in more than 88 % of infants . Increased irritability and decreased activity were observed after the third dose in the Pnc9-MenC group . CONCLUSIONS Pnc9-MenC combination vaccine administered to infants at ages 2 , 3 , and 4 months demonstrated reduced group C meningococcal immunogenicity compared with MenC vaccine . The immunogenicity of concomitantly administered Hib and DTwP vaccines was also diminished . The Pnc9-MenC vaccine was safe and immunogenic for all contained pneumococcal serotypes . The reduced MenC immunogenicity may limit the development of the Pnc9-MenC vaccine Background . Pneumococcal polysaccharide/protein conjugate vaccines ( PnCV ) are immunogenic and effective in infancy . However , an addition to the nine currently recommended vaccine injections during the first year of life of African children may be a deterrent to participation in a PnCV program . Thus we have evaluated the safety and immunogenicity of a 9-valent PnCV ( Wyeth Lederle Pediatrics and Vaccines ) mixed with diphtheria , tetanus toxoid , cell pertussis and Haemophilus influenzae type b ( TETRAMUNE ) . Methods . Healthy Gambian infants were r and omized at the age of 2 months to receive three doses 1 month apart of either ( 1 ) placebo reconstituted in TETRAMUNE in the right thigh ( control ) or ( 2 ) PnCV in the left thigh and TETRAMUNE in the right thigh ( separate ) or ( 3 ) PnCV reconstituted in TETRAMUNE as a single injection in the right thigh ( combined ) . The vaccines were given together with routine Exp and ed Program on Immunization vaccines . Adverse reactions were recorded after vaccination , and antibody concentrations were measured by enzyme-linked immunosorbent assays . Results . Local in duration and tenderness were observed more commonly at the site of injection of TETRAMUNE than at the site of injection with PnCV after each dose of vaccination . Swelling at the site of injection was encountered more frequently at the site of administration of TETRAMUNE than at the site of administration PnCV ( P < 0.00001 for Doses 1 and 2 and P < 0.0009 for Dose 3 ) . Swelling at the site of administration of TETRAMUNE mixed with PnCV was comparable with that observed for TETRAMUNE alone . Although most mothers reported that the babies “ felt hot ” 24 h after each injection , febrile reactions ( temperature , ≥38 ° C ) were infrequent and resolved with antipyretics . Geometric mean titer for anti-polyribosylribitol phosphate antibody was 11.6 & mgr;g/ml [ 95 % confidence limits ( 95 % CI ) , 9.2 , 14.6 ] in the control group and comparable with 13.3 & mgr;g/ml ( 95 % CI 11.0 , 16.0 ) in the combined group and significantly higher at 17.9 & mgr;g/ml ( 95 % CI 14.7 , 21.9;P = 0.01 ) in the separate group . Geometric mean concentrations of serotype-specific pneumococcal antibodies were higher in the combined group than the separate group for all nine serotypes . Antibody responses to diphtheria and pertussis antigens were similar in all groups . Anti-tetanus toxoid antibody concentrations were lowest in the combined group ( 6.66 IU/ml , 95 % CI 5.77 , 7.68 in the control group ; 5.15 IU/ml , 95 % CI 4.39 , 6.03 in the combined group;P = 0.02 ) . However , all vaccinees achieved protective antibody values . Conclusion . The combination of TETRAMUNE and PnCV is safe and immunogenic To evaluate immune responses , safety and reactogenicity of the concomitant use of DTaP-IPV-Hib and the newly available 7-valent pneumococcal conjugate ( 7VPnC ) vaccines when given as the primary immunization series in early infancy . A total of 231 healthy infants were enrolled at 11 German study centers and r and omized to receive either 7VPnC plus DTaP-IPV-Hib vaccines concomitantly into opposite limbs at age 2 , 3 , 4 and 11 - 15 months ( 7VPnC group ) or DTaP-IPV-Hib vaccine at the same ages plus a 7VPnC " catch-up vaccination " at ages 6 , 7 , 8 and 11 - 15 months ( Control group ) . Blood sample s were drawn before and 4 weeks after the first three vaccine doses and 4 weeks after the fourth dose . Local and general side effects ( i.e. safety ) were solicited by diary cards . Immune responses were determined by ELISA except for antibodies to polioviruses ( neutralization assay ) . Post-dose 3 , a significant antibody response against all seven pneumococcal vaccine-serotypes was observed in the 7VPnC group only . Post-dose 4 geometric mean concentrations ( GMCs ) were similar in both groups . GMCs for other vaccine antigens were comparable between groups except for diphtheria ( higher in the 7VPnC group ) and pertactin ( lower in the 7VPnC group ) , although after three vaccine doses there was a 28-fold rise in GMCs from baseline . Both vaccines were generally well-tolerated although there were minor differences in the frequency of local reactions and somewhat more fever or drowsiness in the 7VPnC group . The use of DTaP-IPV-Hib and the 7VPnC vaccine was safe , well-tolerated and immunogenic when given concomitantly at age 2 , 3 and 4 months or when given separately with 7VPnC as a catch-up vaccination at age 6 , 7 , 8 months and as a concomitant booster immunization at age 11 - 15 months OBJECTIVE To evaluate the safety , immunogenicity , and immunologic memory in young infants of a seven-valent ( 6B , 14 , 19F , 23F , 18C , 4 , 9V ) pneumococcal vaccine conjugated to the outer membrane protein complex of Neisseria meningitidis . VACCINEES : Healthy 2-month-old infants 12- to 15-month-old control infants were recruited from participating private practice s. METHODS Infants ( n = 25 ) were vaccinated at 2 , 4 , and 6 months of age with the conjugated pneumococcal vaccine , followed by a single dose of licensed pneumococcal polysaccharide vaccine ( n = 20 ) at 12 to 15 months of age . Thirteen infants who had not received the investigational pneumococcal conjugate vaccine  served as control subjects and were given a single dose of the licensed pneumococcal polysaccharide vaccine at 12 to 15 months of age . RESULTS The investigational pneumococcal conjugate vaccine was well tolerated by infants . The vaccine was highly immunogenic in young infants , with significant increases in antibody to all seven serotypes after either two or three injections . At 12 to 15 months of age , infants who had been primed with the investigational pneumococcal conjugate vaccine had a brisk immunologic response to the booster injection of the licensed pneumococcal polysaccharide vaccine . Control infants , who received a single primary injection of the licensed pneumococcal polysaccharide vaccine , had negligible immunologic responses to four of the seven serotypes and low responses to the other three types . CONCLUSION The investigational seven-valent pneumococcal conjugate vaccine administered to young infants was well tolerated and highly immunogenic and provided immunologic memory to an injection of the licensed pneumococcal polysaccharide vaccine OBJECTIVE To assess the safety and immunogenicity of three doses of a five-valent ( types 6B , 23F , 14 , 18C , and 19F ) pneumococcal conjugate vaccine ( PCV ) among children younger than 2 years who are and are not infected with human immunodeficiency virus ( HIV ) . METHODS A convenience sample of 18 HIV-infected children 2 years and younger ( mean , 12.9 months ) received three doses ( each separated by 2 months ) of PCV . An additional convenience sample of 33 non-HIV-infected children of virtually identical age , race , and sex as the HIV-infected group were r and omized in a double-blind fashion to receive three doses of PCV or saline placebo .  Safety data were collected for 72 hours after each vaccination . Sera were obtained before each and 1 month after the third vaccination to determine vaccine type-specific immunoglobulin G pneumococcal antibody titers by an enzyme-linked immunosorbent assay . RESULTS Seventeen HIV- and 30 non-HIV-infected children completed the study . The PCV was well tolerated by both HIV- and non-HIV-infected children . No significant differences in local or systemic reactions were noted between HIV- and non-HIV-infected PCV or placebo recipients . Three doses of PCV were immunogenic , as evidence d by 16- to 659-fold increases in type-specific geometric mean antibody titers over prevaccination levels in HIV- and non-HIV-infected children . With respect to an arbitrary protective level , 78 % of the antibody titers from HIV-infected children and 88 % of the titers from non-HIV-infected children were 1.0 microgram/mL or greater 1 month after the third PCV dose . HIV-infected children with milder disease ( Centers for Disease Control and Prevention classes N1 - 2 , A1 - 2 , and B1 ) were more likely to have protective antibody titers after the first and second PCV doses than HIV-infected children with more advanced disease ( Centers for Disease Control and Prevention classes N3 , A3 , B2 - 3 , and C1 - 3 ) . However , after the third PCV dose , these differences disappeared . CONCLUSION Three doses of PCV seem safe and immunogenic in both HIV- and non-HIV-infected children younger than 2 years . This type of vaccine should result in a marked reduction in systemic pneumococcal disease in both HIV- and non-HIV-infected children . Given the high incidence of invasive pneumococcal disease in HIV-infected children , this vaccine may markedly improve the quality of life for this unfortunate group of children
A 7-valent pneumococcal polysaccharide-protein conjugate vaccine ( PCV7 ) was licensed in the United States of America in 2000 , but no comprehensive postmarketing review of safety has been carried out .
We conducted a systematic review of the safety of PCV7 and other pneumococcal conjugate vaccines .