An open-label, randomized, multi-center study of the immunogenicity and safety of DTaP-IPV (Kinrix™) co-administered with MMR vaccine with or without varicella vaccine in healthy pre-school age children. Safety and immunogenicity of inactivated poliovirus vaccine when given with measles-rubella combined vaccine and yellow fever vaccine and when given via different administration routes: a phase 4, randomised, non-inferiority trial in The Gambia. Boosting Immune Responses Following Fractional-Dose Inactivated Poliovirus Vaccine: A Randomized, Controlled Trial Inactivated poliovirus vaccine given alone or in a sequential schedule with bivalent oral poliovirus vaccine in Chilean infants: a randomised, controlled, open-label, phase 4, non-inferiority study. Immunogenicity of supplemental doses of poliovirus vaccine for children aged 6-9 months in Moradabad, India: a community-based, randomised controlled trial. Priming after a fractional dose of inactivated poliovirus vaccine. Randomized controlled study of fractional doses of inactivated poliovirus vaccine administered intradermally with a needle in the Philippines. Comparative reactogenicity and immunogenicity of booster doses of diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine and diphtheria-tetanus-inactivated poliovirus vaccine in preadolescents. Randomized controlled clinical trial of fractional doses of inactivated poliovirus vaccine administered intradermally by needle-free device in Cuba. Comparison of the Immunogenicity of Various Booster Doses of Inactivated Polio Vaccine Delivered Intradermally Versus Intramuscularly to HIV-Infected Adults. Primary and booster vaccination with an inactivated poliovirus vaccine (IPV) is immunogenic and well-tolerated in infants and toddlers in China. Intradermal fractional booster dose of inactivated poliomyelitis vaccine with a jet injector in healthy adults. Early priming with inactivated poliovirus vaccine (IPV) and intradermal fractional dose IPV administered by a microneedle device: A randomized controlled trial. Increased Female-Male Mortality Ratio Associated With Inactivated Polio and Diphtheria-Tetanus-Pertussis Vaccines: Observations From Vaccination Trials in Guinea-Bissau Fractional doses of inactivated poliovirus vaccine in Oman. Safety and immunogenicity of inactivated poliovirus vaccine based on Sabin strains with and without aluminum hydroxide: a phase I trial in healthy adults. Attitudes and perceptions of private pediatricians regarding polio immunization in India. Immune response of infants to fractional doses of intradermally administered inactivated poliovirus vaccine. Immune responses after fractional doses of inactivated poliovirus vaccine using newly developed intradermal jet injectors: a randomized controlled trial in Cuba. Boosting of Mucosal Immunity After Fractional-Dose Inactivated Poliovirus Vaccine Poliovirus Type 2 Seroprevalence Following Full- or Fractional-Dose Inactivated Poliovirus Vaccine in the Period After Sabin Type 2 Withdrawal in Sri Lanka.
BACKGROUND In the US , it is recommended that 4 - 6 year old children receive diphtheria-tetanus-acellular pertussis ( DTaP ) , inactivated poliovirus ( IPV ) , measles-mumps-rubella ( MMR ) , varicella ( V ) , and influenza vaccines . Data relating to the concomitant administration of combination DTaP-IPV vaccine ( Kinrix ™ ; GlaxoSmithKline Biologicals ) and influenza or V vaccines are currently limited . This study was undertaken to evaluate the immunogenicity and reactogenicity of Kinrix ™ when co-administered with MMR ( M-M-RII ( ® ) , Merck & Co. ) and Varivax ™ ( Merck & Co. ) in 4 - 6 year old children . METHODS Phase IIIb , open-label , non-inferiority study ( NCT00871117 ) . We r and omized ( 1:1 ) healthy 4 - 6 year olds to receive Kinrix ™ +MMR+V on day 0 ( Group 1 ) , or Kinrix ™ +MMR on day 0 , followed by V at month 1 ( Group 2 ) . We measured  DTaP-IPV immunogenicity before and 1 month post-vaccination ( prior to V vaccination in Group 2 ) . We collected local and general solicited symptoms within 4 days after vaccination and serious adverse events ( SAEs ) through 6 months post-vaccination . RESULTS We enrolled 478 subjects . One month post-vaccination , > 95 % of subjects in both groups had booster responses to diphtheria , tetanus and pertussis antigens and all subjects had seroprotective anti-poliovirus antibody titers . Immune responses in Group 1 were non-inferior to Group 2 for responses to DTaP-IPV antigens according to pre-specified criteria . Reporting of solicited local events at the DTaP-IPV site appeared to be similar between the two vaccine groups , as was reporting of solicited general adverse events within 4 days of vaccination ; no vaccine related SAEs were reported . CONCLUSION Concomitant administration of varicella vaccine with Kinrix ™ and MMR  did not impact the immunogenicity of diphtheria , tetanus , pertussis or poliovirus antigens . Both vaccine regimens were well tolerated . These results support the co-administration of DTaP-IPV , MMR , and V vaccines in 4 - 6-year-old children , providing protection against multiple diseases in a timely and efficient manner BACKGROUND The introduction of the inactivated poliovirus vaccine ( IPV ) represents a crucial step in the polio eradication endgame . This trial examined the safety and immunogenicity of IPV given alongside the measles-rubella and yellow fever vaccines at 9 months and when given as a full or fractional dose using needle and syringe or disposable-syringe jet injector . METHODS We did a phase 4 , r and omised , non-inferiority trial at three periurban government clinics in west Gambia . Infants aged 9 - 10 months who had already received oral poliovirus vaccine were r and omly assigned to receive the IPV , measles-rubella , and yellow fever vaccines , singularly or in combination . Separately , IPV was given as a full intramuscular or fractional intradermal dose by needle and syringe or disposable-syringe jet injector at a second visit . The primary outcomes were seroprevalence rates for poliovirus 4 - 6 weeks post-vaccination and the rate of seroconversion between baseline and post-vaccination serum sample s for measles , rubella , and yellow fever ; and the post-vaccination antibody titres generated against each component of the vaccines . We did a per- protocol analysis with a non-inferiority margin of 10 % for poliovirus seroprevalence and measles , rubella , and yellow fever seroconversion , and ( 1/3 ) log2 for log2-transformed antibody titres . This trial is registered with Clinical Trials.gov , number NCT01847872 . FINDINGS Between July 10 , 2013 , and May 8 , 2014 , we assessed 1662 infants for eligibility , of whom 1504 were enrolled into one of seven groups for vaccine interference and one of four groups for fractional dosing and alternative route of administration . The rubella and yellow fever antibody titres were reduced by co-administration but the seroconversion rates achieved non-inferiority in both cases ( rubella , -4·5 % [ 95 % CI -9·5 to -0·1 ] ; yellow fever , 1·2 % [ -2·9 to 5·5 ] ) . Measles and poliovirus responses were unaffected ( measles , 6·8 % [ 95 % CI -1·4 to 14·9 ] ; poliovirus serotype 1 , 1·6 % [ -6·7 to 4·7 ] ; serotype 2 , 0·0 % [ -2·1 to 2·1 ] ; serotype 3 , 0·0 % [ -3·8 to 3·9 ] ) . Poliovirus seroprevalence was universally high ( > 97 % ) after vaccination , but the antibody titres generated by fractional intradermal doses of IPV did not achieve non-inferiority compared with full dose . The number of infants who seroconverted or had a four-fold rise in titres was also lower by the intradermal route . There were no safety concerns . INTERPRETATION The data support the future co-administration of IPV , measles-rubella , and yellow fever vaccines within the Exp and ed Programme on Immunization schedule at 9 months . The administration of single fractional intradermal doses of IPV by needle and syringe or disposable-syringe jet injector compromises the immunity generated , although it results in a high post-vaccination poliovirus seroprevalence . FUNDING Bill & Melinda Gates Foundation Background Fractional-dose administration of inactivated poliovirus vaccine ( fIPV ) could increase IPV affordability and stretch limited supplies . We assessed immune responses following fIPV administered intradermally , compared with full-dose IPV administered intramuscularly , among adults with a history of oral poliovirus vaccine ( OPV ) receipt . Methods We conducted a r and omized , controlled noninferiority trial in Cuba .  fIPV or IPV were administered on days 0 and 28 ; serum was collected on days 0 , 7 , 28 , and 56 for analysis by a neutralization assay . The primary end point was seroconversion or a ≥4-fold rise in antibody titer . The noninferiority limit was 10 % . The secondary end point was safety , assessed by the number and intensity of adverse reactions . Results A total of 503 of 534 enrolled participants ( 94.2 % ) completed all study requirements . Twenty-eight days after the first dose , 94.8 % , 98.0 % , and 98.0 % of fIPV recipients had an immune response to poliovirus types 1 , 2 , and 3 , respectively , compared with 98.1 % ( P = .06 ) , 98.0 % ( P = 1.00 ) , and 99.2 % ( P = .45 ) in the IPV arm . Noninferiority was achieved on days 7 , 28 , and 56 for all serotypes . No serious adverse events were reported . Conclusion fIPV induced similar boosting immune responses , compared with full-dose IPV . This suggests that fIPV would be an effective strategy to boost population immunity in an outbreak situation . Clinical Trials Registration ACTRN12615000305527 BACKGROUND Bivalent oral poliovirus vaccine ( bOPV ; types 1 and 3 ) is expected to replace trivalent OPV ( tOPV ) globally by April , 2016 , preceded by the introduction of at least one dose of inactivated poliovirus vaccine ( IPV ) in routine immunisation programmes to eliminate vaccine-associated or vaccine-derived poliomyelitis from serotype 2 poliovirus . Because data are needed on sequential IPV-bOPV schedules , we assessed the immunogenicity of two different IPV-bOPV schedules compared with an all-IPV schedule in infants . METHODS We did a r and omised , controlled , open-label , non-inferiority trial with healthy , full-term ( > 2·5 kg birthweight ) infants aged 8 weeks ( ± 7 days ) at six well-child clinics in Santiago , Chile . We used supplied lists to r and omly assign infants ( 1:1:1 ) to receive three polio vaccinations ( IPV by injection or bOPV as oral drops ) at age 8 , 16 , and 24 weeks in one of three sequential schedules : IPV-bOPV-bOPV , IPV-IPV-bOPV , or IPV-IPV-IPV . We did the r and omisation with blocks of 12 stratified by study site . All analyses were done in a masked manner . Co- primary outcomes were non-inferiority of the bOPV-containing schedules compared with the all-IPV schedule for seroconversion ( within a 10 % margin ) and antibody titres ( within two-thirds log2 titres ) to poliovirus serotypes 1 and 3 at age 28 weeks , analysed in the per- protocol population . Secondary outcomes were seroconversion and titres to serotype 2 and faecal shedding for 4 weeks after a monovalent OPV type 2 challenge at age 28 weeks . Safety analyses were done in the intention-to-treat population . This trial is registered with Clinical Trials.gov , number NCT01841671 , and is closed to new participants . FINDINGS Between April 25 and August 1 , 2013 , we assigned 570 infants to treatment : 190 to IPV-bOPV-bOPV  , 192 to IPV-IPV-bOPV  , and 188  to IPV-IPV-IPV . 564 ( 99 % ) were vaccinated and included in the intention-to-treat cohort , and 537 ( 94 % ) in the per- protocol analyses . In the IPV-bOPV-bOPV , IPV-IPV-bOPV , and IPV-IPV-IPV groups , respectively , the proportions of children with seroconversion to type 1 poliovirus were 166 ( 98·8 % ) of 168 , 95 % CI 95·8 - 99·7 ; 178 ( 100 % ) , 97·9 - 100·0 ; and 175 ( 100 % ) , 97·9 - 100·0 . Proportions with seroconvsion to type 3 poliovirus were 163 ( 98·2 % ) of 166 , 94·8 - 99·4 ; 177 ( 100 % ) , 97·9 - 100·0 , and 172 ( 98·9 % ) of 174 , 95·9 - 99·7 . Non-inferiority was thus shown for the bOPV-containing schedules compared with the all-IPV schedule , with no significant differences between groups . In the IPV-bOPV-bOPV , IPV-IPV-bOPV , and IPV-IPV-IPV  groups , respectively , the proportions of children with seroprotective antibody titres to type 1 poliovirus were 168 ( 98·8 % ) of 170 , 95 % CI 95·8 - 99·7 ; 181 ( 100 % ) , 97·9 - 100·0 ; and 177 ( 100 % ) , 97·9 - 100·0 . Proportions to type 3 poliovirus were 166 ( 98·2 % ) of 169 , 94·9 - 99·4 ; 180 ( 100 % ) , 97·9 - 100·0 ; and 174 ( 98·9 % ) of 176 , 96·0 - 99·7 . Non-inferiority comparisons could not be done for this outcome because median titres for the groups receiving OPV were greater than the assay 's upper limit of detection ( log2 titres > 10·5 ) . The proportions of children seroconverting to type 2 poliovirus in the IPV-bOPV-bOPV , IPV-IPV-bOPV , and IPV-IPV-IPV groups , respectively , were 130 ( 77·4 % ) of 168 , 95 % CI 70·5 - 83·0 ; 169 ( 96·0 % ) of 176 , 92·0 - 98·0 ; and 175 ( 100 % ) , 97·8  - 100 . IPV-bOPV schedules result ed in almost a 0·3 log reduction of type 2 faecal shedding compared with the IPV-only schedule . No participants died during the trial ; 81 serious adverse events were reported , of which one was thought to be possibly vaccine-related ( intestinal intussusception ) . INTERPRETATION Seroconversion rates against polioviruses types 1 and 3 were non-inferior in sequential schedules containing IPV and bOPV , compared with an all-IPV schedule , and proportions of infants with protective antibodies were high after all three schedules . One or two doses of bOPV after IPV  boosted intestinal immunity for poliovirus type 2 , suggesting possible cross protection . Additionally , there was evidence of humoral priming for type 2 from one dose of IPV . Our findings could give policy makers flexibility when choosing a vaccination schedule , especially when trying to eliminate vaccine-associated and vaccine-derived poliomyelitis . FUNDING Bill & Melinda Gates Foundation BACKGROUND The continued presence of polio in northern India poses challenges to the interruption of wild poliovirus transmission and the management of poliovirus risks in the post-eradication era . We aim ed to assess the current immunity profile after routine doses of trivalent oral poliovirus vaccine ( OPV ) and numerous supplemental doses of type-1 monovalent OPV ( mOPV1 ) , and compared the effect of five vaccine formulations and dosages on residual immunity gaps . METHODS We did a community-based , r and omised controlled trial of healthy infants aged 6 - 9 months at ten sites in Moradabad , India .  Serum neutralising antibody was measured before infants were r and omly assigned to a study group and given st and ard-potency or higher-potency mOPV1 , intradermal fractional-dose inactivated poliovirus vaccine ( IPV , GlaxoSmithKline ) , or intramuscular full-dose IPV from two different manufacturers ( GlaxoSmithKline or Panacea ) . Follow-up sera were taken at days 7 and 28 . Our primary endpoint was an increase of more than four times in antibody titres . We did analyses by per- protocol in children with a blood sample available before , and 28 days after , receiving study vaccine ( or who completed study procedures ) . This trial is registered with Current Controlled Trials , number IS RCT N90744784 . FINDINGS Of 1002 children enrolled , 869 ( 87 % ) completed study procedures ( ie , blood sample available at day 0 and day 28 ) . At baseline , 862 ( 99 % ) , 625 ( 72 % ) , and 418 ( 48 % ) had detectable antibodies to poliovirus types 1 , 2 , and 3 , respectively . In children who were type-1 seropositive , an increase of more than four times in antibody titre was detected 28 days after they were given st and ard-potency mOPV1 ( 5/13 [ 38 % ] ) , higher-potency mOPV1 ( 6/21 [ 29 % ] ) , intradermal IPV ( 9/16 [ 56 % ] ) , GlaxoSmithKline intramuscular IPV ( 19/22 [ 86 % ] ) , and Panacea intramuscular IPV ( 11/13 [ 85 % ] ) . In those who were type-2 seronegative , 42 ( 100 % ) of 42 seroconverted after GlaxoSmithKline intramuscular IPV , and 24 ( 59 % ) of 41 after intradermal IPV ( p<0·0001 ) . 87 ( 90 % ) of 97 infants who were type-3 seronegative seroconverted after intramuscular IPV , and 21 ( 36 % ) of 49 after intradermal IPV ( p<0·0001 ) . INTERPRETATION Supplemental mOPV1 result ed in almost total seroprevalence against poliovirus type 1 , which is consistent with recent absence of poliomyelitis cases ; whereas seroprevalence against types 2 and 3 was expected for routine vaccination histories . The immunogenicity of IPV produced in India ( Panacea ) was similar to that of an internationally manufactured IPV ( GSK ) . Intradermal IPV was less immunogenic BACKGROUND To reduce the costs of maintaining a poliovirus immunization base in low-income areas , we assessed the extent of priming immune responses after the administration of inactivated poliovirus vaccine ( IPV ) . METHODS We compared the immunogenicity and reactogenicity of a fractional dose of IPV ( one fifth of a full dose ) administered intradermally with a full dose administered intramuscularly in Cuban infants at the ages of 4 and 8 months . Blood was collected from infants at the ages of 4 months , 8 months , 8 months 7 days , and 8 months 30 days to assess single-dose seroconversion , single-dose priming of immune responses , and two-dose seroconversion . Specimens were tested with a neutralization assay . RESULTS A total of 320 infants underwent r and omization , and 310 infants ( 96.9 % ) fulfilled the study requirements . In the group receiving the first fractional dose of IPV , seroconversion to poliovirus types 1 , 2 , and 3 occurred in 16.6 % , 47.1 % , and 14.7 % of participants , respectively , as compared with 46.6 % , 62.8 % , and 32.0 % in the group receiving the first full dose of IPV ( P<0.008 for all comparisons ) . A priming immune response to poliovirus types 1 , 2 , and 3 occurred in 90.8 % , 94.0 % , and 89.6 % of participants , respectively , in the group receiving the fractional dose as compared with 97.6 % , 98.3 % , and 98.1 % in the group receiving the full dose ( P=0.01 for the comparison with type 3 ) . After the administration of the second dose of IPV in the group receiving fractional doses , cumulative two-dose seroconversion to poliovirus types 1 , 2 , and 3 occurred in 93.6 % , 98.1 % , and 93.0 % of participants , respectively , as compared with 100.0 % , 100.0 % , and 99.4 % in the group receiving the full dose ( P<0.006 for the comparisons of types 1 and 3 ) . The group receiving intradermal injections had the greatest number of adverse events , most of which were minor in intensity and none of which had serious consequences . CONCLUSIONS This evaluation shows that vaccinating infants with a single fractional dose of IPV can induce priming and seroconversion in more than 90 % of immunized infants . ( Funded by the World Health Organization and the Pan American Health Organization ; Australian New Zeal and Clinical Trials Registry number , ACTRN12610001046099 . ) OBJECTIVE Comparison of a fractional inactivated poliovirus vaccine ( IPV ) dose administered intradermally ( ID ) to a full dose administered intramuscularly ( IM ) . METHODS Healthy Filipino infants were r and omized to receive IPV as either a fractional ( 1/5(th ) ) dose ID by needle injection or a full dose IM at 6 , 10 , and 14 weeks and a booster at 15 - 18 months of age . Pre- and post-vaccination anti-polio 1 , 2 , and 3 titers were estimated . Adverse events were monitored throughout the study . RESULTS Following primary series vaccination , anti-polio 1 , 2 , and 3 titers were ≥8 ( 1/dil ) in 99 - 100 % of participants , and the ID route was non-inferior to the IM route . Depending on the study group , antibody persistence was detected in 83 - 100 % of participants , and the booster dose result ed in a strong anamnestic response in all groups . The incidence of adverse events in each group was similar , except for injection-site erythema ( higher in the ID group ) . CONCLUSIONS Primary series and booster vaccination of a fractional IPV dose administered by the ID route was highly immunogenic and well tolerated . These data confirm the medical validity of using fractional ID doses of IPV . The programmatic feasibility of implementing affordable mass vaccination programs based on this delivery mode has yet to be established BACKGROUND The changing epidemiology of pertussis in France has emphasized the need for booster vaccinations in adolescents . Although not previously recommended because of the high reactogenicity of whole cell pertussis in children older than 2 years old , the development of less reactogenic acellular pertussis vaccines means that this recommendation may be reconsidered . OBJECTIVES Assessment of the reactogenicity and immunogenicity of a diphtheria-tetanus-acellular pertussis-inactivated poliovirus ( DTPa-IPV = Group 1 ) vaccine administered as the fifth dose in preadolescents in comparison with a commercial diphtheria-tetanus-inactivated poliovirus ( DT-IPV ) ( Group 2 ) vaccine currently recommended for this age group . MATERIAL S AND METHODS An open , r and omized study involving 115 healthy subjects ages 10 to 13 years previously vaccinated with 4 doses of diphtheria-tetanus-whole cell pertussis-IPV vaccines .  Reactogenicity was assessed for 4 days postvaccination using diary cards . Immunogenicity based on antibody assays in sera taken before and 1 month postvaccination was evaluated for all vaccine antigen components . RESULTS Both vaccines showed good tolerability , local and general reactogenicity being similar . For local reactions Group 1=88.1 % and Group 2=86.8 % , and for general reactions Group 1=40.7 % and Group 2=47.2 % . Headache was the most frequent general symptom with 27.1 % for DTPa-IPV and 39.6 % for DT-IPV . The incidence of fever was 5.1 % with DTPa-IPV and 9.4 % for DT-IPV . Good immune responses were obtained against all vaccine components . CONCLUSIONS The inclusion of acellular pertussis did not significantly increase the reactogenicity of DTPa-IPV in comparison with the currently recommended DT-IPV vaccine when given as a fifth dose in preadolescents . To prevent recent resurgence of pertussis in France , this vaccine should be preferred as the booster dose of DTPa-IPV at 11 to 13 years of age as recently approved by the National Council of Hygiene of France BACKGROUND As part of an evaluation of strategies to make inactivated poliovirus vaccine ( IPV ) affordable for developing countries , we conducted a clinical trial of fractional doses of IPV  in Cuba . METHODS We compared the immunogenicity and reactogenicity of fractional-dose IPV ( 0.1 mL , or 1/5 of a full dose ) given intradermally using a needle-free jet injector device compared with full doses given intramuscularly . Subjects were r and omized at birth to receive IPV at 6 , 10 , and 14 weeks . RESULTS A total of 471 subjects were r and omized to the 2 study groups , and 364 subjects fulfilled the study requirements . No significant differences at baseline were detected . Thirty days after completing the 3-dose schedule of IPV , 52.9 % , 85.0 % , and 69.0 % of subjects in the fractional-dose IPV arm seroconverted for poliovirus types 1 , 2 , and 3 , respectively , whereas 89.3 % , 95.5 % , and 98.9 % of subjects in the full-dose IPV arm seroconverted for poliovirus types 1 , 2 , and 3 , respectively ( all comparisons , P < .001 ) . The median titers of each poliovirus serotype were significantly lower in the intradermal arm than in the intramuscular arm ( P < .001 ) . Only minor local adverse effects and no moderate or serious adverse events were reported . CONCLUSIONS This large-scale evaluation demonstrates the feasibility of fractional doses of IPV given intradermally as an antigen-sparing strategy but also shows that IPV given to infants at 6 , 10 , and 14 weeks of age results in suboptimal immunogenicity ( especially for the fractional-dose arm ) BACKGROUND Inactivated polio vaccine ( IPV ) is necessary for global polio eradication because oral polio vaccine can rarely cause poliomyelitis as it mutates and may fail to provide adequate immunity in immunocompromised population s. However , IPV is unaffordable for many developing countries . Intradermal IPV shows promise as a means to decrease the effective dose and cost of IPV , but prior studies , all using 20 % of the st and ard dose used in intramuscular IPV , result ed in inferior antibody titers . METHODS We r and omly assigned 231 adults with well-controlled human immunodeficiency virus infection at a ratio of 2:2:2:1 to receive 40 % of the st and ard dose of IPV intradermally , 20 % of the st and ard dose intradermally , the full st and ard dose intramuscularly , or 40 % of the st and ard dose intramuscularly . Intradermal vaccination was done using the NanoPass MicronJet600 microneedle device . RESULTS Baseline immunity was 87 % , 90 % , and 66 % against poliovirus serotypes 1 , 2 , and 3 , respectively . After vaccination , antibody titers increased a median of 64-fold . Vaccine response to 40 % of the st and ard dose administered intradermally was comparable to that of the st and ard dose of IPV administered intramuscularly and result ed in higher ( although not significantly ) antibody titers . Intradermal administration had higher a incidence of local side effects ( redness and itching ) but a similar incidence of systemic side effects and was preferred by study participants over intramuscular administration . CONCLUSIONS A 60 % reduction in the st and ard IPV dose without reduction in antibody titers is possible through intradermal administration INTRODUCTION Replacing live-attenuated oral poliovirus vaccines ( OPV ) with inactivated poliovirus vaccines ( IPV ) is part of the global strategy to eradicate poliomyelitis . China was declared polio-free in 2000 but continues to record cases of vaccine-associated-poliomyelitis and vaccine-derived-poliovirus outbreaks . Two pilot safety studies and two larger immunogenicity trials evaluated the non-inferiority of IPV ( Poliorix ™ , GSK Vaccines , Belgium ) versus OPV in infants and booster vaccination in toddlers primed with either IPV or OPV in China . METHODS In pilot safety studies , 25 infants received 3-dose IPV primary vaccination  ( Study A , www . clinical trial.gov NCT00937404 ) and 25 received an IPV booster after priming with three OPV doses ( Study B , NCT01021293 ) . In the r and omised , controlled immunogenicity and safety trial ( Study C , NCT00920439 ) , infants received 3-dose primary vaccination with IPV ( N=541 ) or OPV ( N=535 ) at 2,3,4 months of age , and a booster IPV dose at 18 - 24 months ( N=470 , Study D , NCT01323647 : extension of study C ) . Blood sample s were collected before and one month post-dose-3 and booster . Reactogenicity was assessed using diary cards . Serious adverse events ( SAEs ) were captured throughout each study . RESULTS Study A and B showed that IPV priming and IPV boosting ( after OPV ) was safe . Study C : One month post-dose-3 , all IPV and ≥ 98.3 % OPV recipients had seroprotective antibody titres towards each poliovirus type . The immune response elicited by IPV was non-inferior to Chinese OPV . Seroprotective antibody titres persisted in ≥ 94.7 % IPV and ≥ 96.1 % OPV recipients at 18 - 24 months ( Study D ) . IPV had a clinical ly acceptable safety profile in all studies . Grade 3 local and systemic reactions were uncommon . No SAEs were related to IPV administration . CONCLUSION Trivalent IPV is non-inferior to OPV in terms of seroprotection ( in the Chinese vaccination schedule ) in infant and toddlers , with a clinical ly acceptable safety profile For global eradication of poliomyelitis , inactivated poliovirus vaccine ( IPV ) needs to become available in all countries . Using fractional-doses ( reduced-doses ) may impact affordability and optimize the utilization of the production capacity . Intradermal administration has the potential to lower the dose without reducing immunogenicity . A needle-free jet injector may be a reliable way to administer vaccines intradermally . The primary objective of this r and omized controlled trial was to compare the immunogenicity and tolerability of fractional-dose intradermal IPV ( Netherl and s Vaccine Institute , NVI ) booster vaccination administered with a jet injector ( PharmaJet ) to full-dose and fractional-dose intramuscular vaccination with a needle and syringe .  Immunogenicity was assessed by comparing the differences in the post-vaccination log2 geometric mean concentrations of neutralizing antibodies ( GMC ) between the study groups . A total of 125 Dutch adult volunteers with a well-documented vaccination history were r and omized to one of four groups : full-dose intramuscular needle ( IM-NS-0.5 ) , full-dose intramuscular jet injector ( IM-JI-0.5 ) , 1/5th dose intramuscular needle ( IM-NS-0.1 ) , 1/5th dose intradermal jet injector ( ID-JI-0.1 ) . Vaccination with the JI was less painful ( 87 % no pain ) than vaccination with a NS ( 60 % no pain ) , but caused more transient erythema ( JI 85 % , NS 24 % ) and swelling ( JI 50 % , NS 5 % ) . Intradermal vaccination caused less vaccination site soreness ( ID 16 % , IM 52 % ) . At baseline all subjects had seroprotective antibody concentrations . After 28 days , GMC were slightly lower in the ID-JI-0.1 group than in the reference group ( IM-NS-0.5 ) . The differences were not statistically significant , but the stringent non-inferiority criterion ( i.e. a difference of 1 serum dilution in the microneutralization assay ) was not met . After one year , differences in GMC were no longer apparent . In contrast , intramuscular vaccination with a fractional dose administered with a needle ( IM-NS-0.1 ) was statistically inferior to full-dose intramuscular vaccination . This shows that intradermal but not intramuscular delivery of fractional-dose IPV may be sufficient for routine polio vaccination INTRODUCTION Inactivated poliovirus vaccine ( IPV ) introduction and phased oral poliovirus vaccine ( OPV ) cessation are essential for eradication of polio . METHODS Healthy 6-week old infants in Bangladesh were r and omized to one of five study arms : receipt of trivalent OPV ( tOPV ) or bivalent OPV ( bOPV ) at ages 6 , 10 and 14 weeks , intramuscular IPV or intradermal one-fifth fractional dose IPV ( f-IPV ) at ages 6 and 14 weeks , or f-IPV at ages 6 and 14 weeks with bOPV at age 10 weeks ( f-IPV/bOPV ) . All participants received tOPV at age 18 weeks . RESULTS Of 975 infants r and omized , 95 % ( 922 ) completed follow-up . Type 1 seroconversion after 3 doses at 6 , 10 and 14 weeks was higher with bOPV compared with tOPV ( 99 % vs 94 % , p=0.019 ) . Seroconversions to types 1 and 3 after 2 IPV doses at ages 6 and 14 weeks were no different than after 3 doses of tOPV or bOPV at ages 6 , 10 and 14 weeks . A priming response , seroconversion 1 week after IPV at 14 weeks among those who did not seroconvert after IPV at 6 weeks , was observed against poliovirus types 1 , 2 and 3 in 91 % , 84 % and 97 % , respectively . Compared with IPV , f-IPV failed non-inferiority tests for seroconversion with 1 or 2 doses and priming after 1 dose . DISCUSSION The findings demonstrate considerable priming with IPV at age 6 weeks , comparable immunogenicity of tOPV and bOPV , and inferior immunogenicity of one-fifth f-IPV compared with IPV . If IPV induced priming at age 6 weeks is similar to that at age 14 weeks , IPV could be administered at a younger age and possibly with a higher coverage Background : The 2-fold increase in female mortality after high-titer measles vaccine may have occurred because many children received diphtheria-tetanus-pertussis ( DTP ) vaccine or inactivated polio vaccine ( IPV ) after high-titer measles vaccine . Objective : We examined whether DTP vaccine and IPV were associated with increased female mortality when they were the most recent vaccine administered to children who had not received measles vaccine . Setting and Design : IPV was used as a control vaccine in 4 r and omized trials of early measles vaccination ( MV ) with enrollment at 4–6 months of age conducted in Guinea-Bissau . Many children had not received all 3 DTP vaccinations before enrollment , and therefore received DTP after IPV or MV . We examined whether DTP vaccination status at enrollment affected the female-male mortality ratio . Population : 9544 children enrolled in 4 trials . Main outcome measure : The female-male mortality ratio in different vaccine groups . Results : Females had a higher mortality rate than males among children r and omized to receive IPV ( mortality rate ratio [ MR ] 1.52 , 95 % CI 1.02–2.28 ) , but females had a similar mortality rate to males among children r and omized to receive MV ( MR 1.01 , 0.69–1.46 ) and among children in the IPV group after they had received MV at 9 months of age or later ( MR 0.88 , 0.68–1.14 ) . Children who had not received a third dose of DTP before enrollment ( and were likely to receive DTP after MV or IPV ) tended to have a higher mortality than children who had received all 3 doses of DTP ( MR 1.30 , 0.97–1.73 ) . This effect was seen only among girls ( MR 1.61 , 1.08–2.40 ) and not among boys ( MR 1.02 , 0.67–1.54 ) . Girls had a lower mortality when MV was the most recent vaccine received rather than DTP or IPV ( MR 0.49 , 0.28–0.87 ) . Conclusions : R and omization to IPV was associated with higher female than male mortality . However , the increased female mortality might result from additional doses of DTP received after enrollment and before measles vaccination BACKGROUND We conducted a clinical trial of fractional doses of inactivated poliovirus vaccine administered to infants in Oman , in order to evaluate strategies for making the vaccine affordable for use in developing countries . METHODS We compared fractional doses of inactivated poliovirus vaccine ( 0.1 ml , representing one fifth of a full dose ) given intradermally with the use of a needle-free jet injector device , with full doses of vaccine given intramuscularly , with respect to immunogenicity and reactogenicity . Infants were r and omly assigned at birth to receive either a fractional dose or a full dose of inactivated poliovirus vaccine at 2 , 4 , and 6 months . We also administered a challenge dose of monovalent type 1 oral poliovirus vaccine at 7 months and collected stool sample s before and 7 days after administration of the challenge dose . RESULTS A total of 400 infants were r and omized , of whom 373 ( 93.2 % ) fulfilled the study requirements . No significant baseline differences between the groups were detected . Thirty days after completion of the three-dose schedule , the rates of seroconversion to types 1 , 2 , and 3 poliovirus were 97.3 % , 95.7 % , and 97.9 % , respectively , in the fractional-dose group , as compared with 100 % seroconversion to all serotypes in the full-dose group ( P=0.01 for the comparison with respect to type 2 poliovirus ; results with respect to types 1 and 3 poliovirus were not significant ) . The median titers were significantly lower in the fractional-dose group than in the full-dose group ( P<0.001 for all three poliovirus serotypes ) . At 7 months , 74.8 % of the infants in the fractional-dose group and 63.1 % of those in full-dose group excreted type 1 poliovirus ( P=0.03 ) . Between birth and 7 months , 42 hospitalizations were reported , all related to infectious causes , anemia , or falls , with no significant difference between vaccination groups . CONCLUSIONS These data show that fractional doses of inactivated poliovirus vaccine administered intradermally at 2 , 4 , and 6 months , as compared with full doses of inactivated poliovirus vaccine given intramuscularly on the same schedule , induce similar levels of seroconversion but significantly lower titers . ( Current Controlled Trials number , IS RCT N17418767 . BACKGROUND An inactivated poliovirus vaccine ( IPV ) based on attenuated poliovirus strains ( Sabin-1 , -2 and -3 ) was developed for technology transfer to manufacturers in low- and middle income countries in the context of the Global Polio Eradication Initiative . METHOD Safety and immunogenicity of the Sabin-IPV was evaluated in a double-blind , r and omized , controlled , phase I ' proof-of-concept ' trial . Healthy male adults received a single intramuscular injection with Sabin-IPV , Sabin-IPV adjuvanted with aluminum hydroxide or conventional IPV . Virus-neutralizing titers against both Sabin and wild poliovirus strains were determined before and 28 days after vaccination . RESULTS No vaccine-related serious adverse events were observed , and all local and systemic reactions were mild or moderate and transient . In all subjects , an increase in antibody titer for all types of poliovirus ( both Sabin and wild strains ) was observed 28 days after vaccination . CONCLUSION Sabin-IPV and Sabin-IPV adjuvanted with aluminum hydroxide administered as a booster dose were equally immunogenic and safe as conventional IPV . EudraCTnr : 2010 - 024581 - 22 , NCT01708720 BACKGROUND India has faced considerable challenges in eradicating polio . Uttar Pradesh ( UP ) and Bihar are the two states in India where transmission of polio has never been interrupted . Private pediatricians are important stakeholders for vaccine delivery and maintaining public confidence in vaccines . The purpose of this study was to investigate the attitudes and perceptions of pediatricians in India regarding polio immunization and their opinions about various strategies regarding polio eradication in the country . METHODS A r and om sample of 785 pediatricians belonging to the Indian Academy of Pediatrics ( IAP ) were selected for the survey with over sampling of members located in Bihar and UP . Potential participants were either contacted by phone or sent a self-administered anonymous question naire by mail . For this analysis both sets of responses were combined . Surveys were conducted from June 2009 to June 2010 . RESULTS A total of 398 surveys were completed ( 51 % ) . Nearly all respondents indicated that polio eradication is still an important priority ( 99.7 % ) . Ninety-six percent of pediatricians believed that strengthening routine immunization efforts remains the best way to eradicate polio in endemic areas . Other measures thought to be important in eradicating polio are mass campaigns with IPV ( 73 % ) and mass campaigns with bivalent OPV ( 59 % ) . Pediatricians also identified several barriers to polio eradication which included parents ' lack of awareness of the importance of polio vaccination ( 88.8 % ) , parents ' lack of confidence in polio vaccine ( 64.0 % ) , religious beliefs ( 59.2 % ) , fear of side effects ( 59.2 % ) , lack of time or priority ( 56.6 % ) , superstition ( 50.3 % ) and cultural beliefs ( 46.4 % ) . CONCLUSION There is still strong support for polio eradication efforts among IAP members . Pediatricians in India strongly believe that improving the coverage of routine immunization remains the best way to eradicate polio . There is an urgent need to improve awareness , build confidence in the program , and remove barriers among parents Seventy eight infants aged 6 - 8 weeks received either two doses of 0.1 ml of inactivated poliovirus vaccine ( IPV ) intradermally 8 weeks apart ( group A ) or three doses 4 weeks apart ( group B ) . Pre- and 4 weeks post-immunization serum sample s were tested for the presence and titer of neutralizing antibody to poliovirus types 1 , 2 and 3 . The seroconversion rates to poliovirus types 1 , 2 and 3 were 90 , 70 and 97 % , respectively , among infants in group A and 90 , 80 and 98 % , respectively , in group B ; in children without pre-existing maternal antibody , seroconversion rates were 100 % to all three poliovirus serotypes in both groups . These rates were comparable to those in children receiving five doses of OPV or two doses of intramuscular IPV . Intradermal administration of fractional doses of IPV may be a less expensive alternative for use in developing countries INTRODUCTION The World Health Organization recommends that , as part of the new polio endgame , a dose of inactivated poliovirus vaccine ( IPV ) be introduced by the end of 2015 in all countries using only oral poliovirus vaccine ( OPV ) . Administration of fractional dose ( 1/5th of full dose ) IPV ( fIPV ) intradermally may reduce costs , but its administration is cumbersome with BCG needle and syringe . We evaluated performance of two newly developed intradermal-only jet injectors and compared the immune response induced by fIPV with that induced by full-dose IPV . METHODS Children between 12 and 20 months of age , who had previously received two doses of OPV , were enrolled in Camaguey , Cuba . Subjects received a single dose of IPV ( either full-dose IPV intramuscularly with needle and syringe or fIPV intradermally administered with one of two new injectors or with BCG needle or a conventional needle-free injector ) . Serum was tested for presence of poliovirus neutralizing antibodies on day 0 ( pre-IPV ) and on days 3 , 7 and 21 ( post-vaccination ) . RESULTS Complete data were available from 74.2 % ( 728/981 ) subjects . Baseline median antibody titers were 713 , 284 , and 113 for poliovirus types 1 , 2 , and 3 , respectively . Seroprevalence at study end were similar across the intervention groups ( ≥ 94.8 % ) . The immune response induced with one new injector was similar to BCG needle and to the conventional injector ; and superior to the other new injector . fIPV induced significantly lower boosting response compared to full-dose IPV . No safety concerns were identified . INTERPRETATION One of the two new injectors demonstrated its ability to streamline intradermal fIPV administration , however , further investigations are needed to assess the potential contribution of fIPV in the polio endgame plan Background Inactivated poliovirus vaccine ( IPV ) boosts mucosal immunity in persons previously vaccinated with oral poliovirus vaccine ( OPV ) . We assessed whether fractional-dose IPV ( fIPV , 1/5th of full dose ) administered intradermally also boosts mucosal immunity . Methods Children 10 - 12 years old were enrolled in Sri Lanka and r and omized to receive one dose IPV , fIPV , or no IPV vaccine . One month later , they received OPV challenge .  Blood was collected at enrolment and before challenge ; stool was collected at 3 , 7 , and 14 days post-challenge . Sera were analysed for presence of poliovirus neutralizing antibodies ; stool was analysed for poliovirus . Results We analysed 304/309 ( 98 % ) enrolled subjects . There were 16/97 ( 16 % ) , 9/99 ( 9 % ) , and 72/95 ( 76 % ) subjects excreting poliovirus after challenge in the IPV , fIPV and " No IPV Vaccine " study arms , respectively ( P < .001 for comparison of IPV [ or fIPV ] vs " No IPV Vaccine " ; P = .1 for comparisons of fIPV vs IPV ) . Relative decrease in excretion prevalence was 80 % and 88 % to IPV and fIPV , respectively , compared with the " No IPV Vaccine " control arm . Conclusions Single fIPV dose boosted mucosal immunity to a similar degree as single full dose of IPV . This finding provides further evidence in support of fIPV for poliovirus outbreak response at the time of IPV global supply shortage . Clinical trials registration Australia New Zeal and Clinical Trial Registry ACTRN12616000124437p BACKGROUND In July 2016 , Sri Lanka replaced 1 intramuscular dose of inactivated poliovirus vaccine ( IPV ) with 2 doses of intradermal fractional-dose IPV ( fIPV ) in its routine immunization schedule . We carried out a survey of seroprevalence of antipolio antibodies in children who received 2 fIPV doses and compared it with those who received 1 full IPV dose . METHODS Children born between March and December 2016 were r and omly selected from 3 Sri Lankan districts ( Colombo , Badulla , and Anuradhapura ) . Serum sample s were collected and tested for presence of neutralizing antibodies to poliovirus types 1 , 2 , and 3 . RESULTS Seroprevalence of antipolio antibodies was 100 % in all districts for poliovirus type 1 and poliovirus type 3 ; it ranged between 90 % and 93 % for poliovirus type 2 ( PV2 ) in children who received 1 full IPV dose and between 78 % and 100 % in those receiving 2 fIPV doses ( P = .22 ) . The median reciprocal titers of anti-PV2 antibodies were similar in children who received full-dose IPV and those who received fIPV ( 1:64 vs 1:45 , respectively ; P = .11 ) . CONCLUSIONS Our study demonstrated not only that Sri Lanka succeeded in maintaining very high primary immunization coverage also but that it is feasible for a national immunization program to implement fIPV immunization and achieve high coverage with intradermal application . The seroprevalence of anti-PV2 antibodies did not decrease after the introduction of fIPV
BACKGROUND Poliomyelitis is a debilitating and deadly infection .
Despite exponential growth in medical science , there is still no cure for the disease , which is caused by three types of wild polioviruses : types 1 , 2 , and 3 .
According to the Global Polio Eradication Initiative ( GPEI ) , wild poliovirus is still in circulation in three countries , and fresh cases have been reported even in the year 2018 .
Due to the administration of live vaccines , the risk for vaccine-derived poliovirus ( VDPV ) is high in areas that are free from wild polioviruses .
This is evident based on the fact that VDPV caused 20 outbreaks between 2000 and 2011 .
Recent recommendations from the World Health Organization favoured the inclusion of inactivated poliovirus vaccine ( IPV ) in the global immunisation schedule .
IPV can be delivered in two ways : intramuscularly and intradermally .
IPV was previously administered intramuscularly , but shortages in vaccine supplies , coupled with the higher costs of the vaccines , led to the innovation of delivering a fractional dose ( one-fifth ) of IPV intradermally .
However , there is uncertainty regarding the efficacy , immunogenicity , and safety of an intradermal , fractional dose of IPV compared to an intramuscular , full dose of IPV .
OBJECTIVES To compare the immunogenicity and efficacy of an inactivated poliovirus vaccine ( IPV )  in equivalent immunisation schedules using fractional-dose IPV given via the intradermal route versus full-dose IPV given via the intramuscular route .