ABSTRACT
OBJECTIVES: This study aims to evaluate the safety of a new inactivated poliomyelitis vaccine (Sabin strains) (sIPV) for large-scale use in primary and booster immunizations, whether simultaneously administered with other vaccines or not and to explore the persistence of all vaccines at approximately six months after vaccination. METHOD: A total of 3200 infants were recruited into this study, including 2000 infants aged 2-3 months randomly assigned (1:1) into the "sIPV basic" or the "sIPV+DTaP" group for primary immunization of sIPV. Another 1200 children aged 18 months old and above were randomly assigned (2:2:1:1) into the "sIPV booster," "sIPV+HepA-I," "sIPV+MMR", or "sIPV+HepA-L" group for booster immunization of sIPV. Adverse events within 30 days of each vaccination dose in all participants were self-reported by guardians using a WeChat mini-program. Approximately 200 blood samples were collected at 5-7 months after the final vaccination to test for antibodies against poliovirus and other viruses. RESULTS: 3198 participants in total were included in the safety study, including 1999 infants aged 2-3 months old and 1199 children aged 18-26 months old. For primary immunization, the incidence of adverse reactions in the "sIPV basic" and the "sIPV+DTaP" group were 3.19 and 6.21% (P = 0.001), respectively. For booster immunization, the incidences of adverse reaction for the "sIPV booster" group were 2.25%, while the incidence for the "sIPV +others" group in total was 2.50% (P = 0.788). Most adverse reactions were mild. Fever was the most common symptom in all groups. No vaccine-related serious adverse events (SAEs) were observed in this study. The seropositivity rates of antibodies in the "sIPV basic" and the "sIPV+DTaP" group were 92.31 and 100% against type 1 poliovirus (P = 0.031); 96.15% and 98.57% against type 2 poliovirus (P = 0.575); 98.08% and 91.43% against type 3 poliovirus (P = 0.237), respectively. Regarding booster vaccination with sIPV, whether co-administered with other vaccines or not, the seropositivity rates of antibodies against the three types of polioviruses were all 100%. Seropositivity rates of antibodies against hepatitis A, measles, mumps, and rubella were all no <77%, except for pertussis, which was <30%. CONCLUSION: sIPV demonstrated good safety and immune persistence for primary and booster vaccinations, whether administered singly or simultaneously. Antibodies against hepatitis A, measles, mumps and rubella were not disrupted by the co-vaccination. However, the seropositivity rates and geometric mean concentrations (GMCs) of antibodies against pertussis indicate the necessity for a booster dose.
Subject(s)
Antibodies, Viral , Immunization, Secondary , Poliomyelitis , Poliovirus Vaccine, Inactivated , Humans , Poliovirus Vaccine, Inactivated/immunology , Poliovirus Vaccine, Inactivated/administration & dosage , Poliovirus Vaccine, Inactivated/adverse effects , Infant , Immunization, Secondary/methods , Male , China , Female , Antibodies, Viral/blood , Poliomyelitis/prevention & control , Poliomyelitis/immunology , Poliovirus/immunology , Immunization Schedule , Vaccination/methods , Vaccines, Combined/immunology , Vaccines, Combined/administration & dosage , Vaccines, Combined/adverse effectsABSTRACT
In 2012, the Strategic Advisory Group of Experts on Immunization (SAGE) recommended introduction of at least one inactivated poliovirus vaccine (IPV) dose in essential immunization programs. We evaluated systemic humoral and intestinal mucosal immunity of a sequential IPV-bivalent oral poliovirus vaccine (bOPV) schedule compared with a co-administration IPV + bOPV schedule in an open-label, randomized, controlled, non-inferiority, inequality trial in Dhaka, Bangladesh. Healthy infants aged 6 weeks were randomized to either: (A) IPV and bOPV at 6 and bOPV at 10 and 14 weeks (IPV + bOPV-bOPV-bOPV); or (B) IPV at 6 and bOPV at 10 and 14 weeks (IPV-bOPV-bOPV). Of 456 participants enrolled and randomly assigned during May-August 2015, 428 (94%) were included in the modified intention-to-treat analysis (arm A: 211, arm B: 217). Humoral immune responses did not differ at 18 weeks between study arms: type 1 (98% versus 96%; p = 0.42), type 2 (37% versus 39%; p = 0.77), and type 3 (97% versus 93%; p = 0.07). Virus shedding one week after the bOPV challenge dose in arm B was non-inferior to arm A (type 1 difference = -3% [90% confidence interval: -6 - 0.4%]; type 3 difference: -3% [-6 to -0.2%]). Twenty-six adverse events including seven serious adverse events were reported among 25 participants including one death; none were attributed to study vaccines. An IPV-bOPV-bOPV sequential schedule induced comparable systemic humoral immunity to all poliovirus types and types 1 and 3 intestinal mucosal immunity as an IPV + bOPV-bOPV-bOPV co-administration schedule.
Subject(s)
Antibodies, Viral , Immunity, Humoral , Immunity, Mucosal , Immunization Schedule , Poliomyelitis , Poliovirus Vaccine, Inactivated , Poliovirus Vaccine, Oral , Humans , Poliovirus Vaccine, Inactivated/immunology , Poliovirus Vaccine, Inactivated/administration & dosage , Poliovirus Vaccine, Inactivated/adverse effects , Poliovirus Vaccine, Oral/administration & dosage , Poliovirus Vaccine, Oral/immunology , Poliovirus Vaccine, Oral/adverse effects , Bangladesh , Male , Female , Infant , Antibodies, Viral/blood , Antibodies, Viral/immunology , Poliomyelitis/prevention & control , Poliomyelitis/immunology , Poliovirus/immunology , Intestinal Mucosa/immunologyABSTRACT
To fully understand the safety of DTaP-IPV/Hib vaccination, we evaluated the differences between DTaP-IPV/Hib co-administration and separate administration of the DTaP, IPV and Hib vaccines (DTaP+IPV+Hib) based on adverse events following immunization (AEFI). All AEFI reported in Hebei Province, China, between 2020 and 2022 were included in this study. The risk difference (RD%), relative risk (RR), and Chi-square value were used to compare the differences in reported rates of AEFI between the DTaP-IPV/Hib and DTaP+IPV+Hib groups. From 2020 to 2022, 130 AEFI cases were reported in Hebei Province after DTaP-IPV/Hib vaccination, corresponding to an AEFI reported rate of 66.9/million doses, which was significantly lower than that for DTaP+IPV+Hib (9836 AEFI with a reported rate of 637.8/million doses). The overall reported rate of non-severe AEFI for DTaP+IPV+Hib vaccines was 9.5 times that of DTaP-IPV/Hib vaccination [95% confidence interval (CI): 8.0, 11.3]. Meanwhile, the reported rate of AEFI among infants aged 0-1 y was 9.8 times higher for DTaP+IPV+Hib than for DTaP-IPV/Hib (95% CI: 8.2, 11.7). DTaP+IPV+Hib vaccination also resulted in higher risks of high fever, localized redness and swelling, localized induration, and allergic rash compared with DTaP-IPV/Hib vaccination. The risk of AEFI, which were mostly mild reaction, was higher after vaccination with DTaP+IPV+Hib than after DTaP-IPV/Hib vaccination.
Subject(s)
Diphtheria-Tetanus-Pertussis Vaccine , Haemophilus Vaccines , Poliovirus Vaccine, Inactivated , Vaccines, Combined , Humans , Haemophilus Vaccines/adverse effects , Haemophilus Vaccines/administration & dosage , Poliovirus Vaccine, Inactivated/adverse effects , Poliovirus Vaccine, Inactivated/administration & dosage , Diphtheria-Tetanus-Pertussis Vaccine/adverse effects , Diphtheria-Tetanus-Pertussis Vaccine/administration & dosage , Infant , Vaccines, Combined/adverse effects , Vaccines, Combined/administration & dosage , China/epidemiology , Female , Male , Vaccination/adverse effects , Haemophilus Infections/prevention & control , Immunization Schedule , Drug-Related Side Effects and Adverse Reactions/epidemiology , Diphtheria-Tetanus-acellular Pertussis Vaccines/adverse effects , Diphtheria-Tetanus-acellular Pertussis Vaccines/administration & dosageSubject(s)
Haemophilus Vaccines , Hepatitis B Vaccines , Parents , Poliovirus Vaccine, Inactivated , Humans , China , Haemophilus Vaccines/economics , Hepatitis B Vaccines/economics , Hepatitis B Vaccines/administration & dosage , Cross-Sectional Studies , Parents/psychology , Poliovirus Vaccine, Inactivated/economics , Poliovirus Vaccine, Inactivated/administration & dosage , Vaccines, Combined/economics , Patient Acceptance of Health Care/psychology , Surveys and Questionnaires , Vaccination/economics , Vaccination/psychology , Diphtheria-Tetanus-Pertussis Vaccine/economics , Diphtheria-Tetanus-Pertussis Vaccine/administration & dosage , InfantABSTRACT
BACKGROUND: In many countries, infant vaccination with acellular pertussis (aP) vaccines has replaced use of more reactogenic whole-cell pertussis (wP) vaccines. Based on immunological and epidemiological evidence, we hypothesised that substituting the first aP dose in the routine vaccination schedule with wP vaccine might protect against IgE-mediated food allergy. We aimed to compare reactogenicity, immunogenicity, and IgE-mediated responses of a mixed wP/aP primary schedule versus the standard aP-only schedule. METHODS AND FINDINGS: OPTIMUM is a Bayesian, 2-stage, double-blind, randomised trial. In stage one, infants were assigned (1:1) to either a first dose of a pentavalent wP combination vaccine (DTwP-Hib-HepB, Pentabio PT Bio Farma, Indonesia) or a hexavalent aP vaccine (DTaP-Hib-HepB-IPV, Infanrix hexa, GlaxoSmithKline, Australia) at approximately 6 weeks old. Subsequently, all infants received the hexavalent aP vaccine at 4 and 6 months old as well as an aP vaccine at 18 months old (DTaP-IPV, Infanrix-IPV, GlaxoSmithKline, Australia). Stage two is ongoing and follows the above randomisation strategy and vaccination schedule. Ahead of ascertainment of the primary clinical outcome of allergist-confirmed IgE-mediated food allergy by 12 months old, here we present the results of secondary immunogenicity, reactogenicity, tetanus toxoid IgE-mediated immune responses, and parental acceptability endpoints. Serum IgG responses to diphtheria, tetanus, and pertussis antigens were measured using a multiplex fluorescent bead-based immunoassay; total and specific IgE were measured in plasma by means of the ImmunoCAP assay (Thermo Fisher Scientific). The immunogenicity of the mixed schedule was defined as being noninferior to that of the aP-only schedule using a noninferiority margin of 2/3 on the ratio of the geometric mean concentrations (GMR) of pertussis toxin (PT)-IgG 1 month after the 6-month aP. Solicited adverse reactions were summarised by study arm and included all children who received the first dose of either wP or aP. Parental acceptance was assessed using a 5-point Likert scale. The primary analyses were based on intention-to-treat (ITT); secondary per-protocol (PP) analyses were also performed. The trial is registered with ANZCTR (ACTRN12617000065392p). Between March 7, 2018 and January 13, 2020, 150 infants were randomised (75 per arm). PT-IgG responses of the mixed schedule were noninferior to the aP-only schedule at approximately 1 month after the 6-month aP dose [GMR = 0·98, 95% credible interval (0·77 to 1·26); probability (GMR > 2/3) > 0·99; ITT analysis]. At 7 months old, the posterior median probability of quantitation for tetanus toxoid IgE was 0·22 (95% credible interval 0·12 to 0·34) in both the mixed schedule group and in the aP-only group. Despite exclusions, the results were consistent in the PP analysis. At 6 weeks old, irritability was the most common systemic solicited reaction reported in wP (65 [88%] of 74) versus aP (59 [82%] of 72) vaccinees. At the same age, severe systemic reactions were reported among 14 (19%) of 74 infants after wP and 8 (11%) of 72 infants after aP. There were 7 SAEs among 5 participants within the first 6 months of follow-up; on blinded assessment, none were deemed to be related to the study vaccines. Parental acceptance of mixed and aP-only schedules was high (71 [97%] of 73 versus 69 [96%] of 72 would agree to have the same schedule again). CONCLUSIONS: Compared to the aP-only schedule, the mixed schedule evoked noninferior PT-IgG responses, was associated with more severe reactions, but was well accepted by parents. Tetanus toxoid IgE responses did not differ across the study groups. TRIAL REGISTRATION: Trial registered at the Australian and New Zealand Clinical 207 Trial Registry (ACTRN12617000065392p).
Subject(s)
Diphtheria-Tetanus-Pertussis Vaccine , Immunization Schedule , Immunoglobulin E , Humans , Infant , Double-Blind Method , Immunoglobulin E/immunology , Immunoglobulin E/blood , Female , Male , Diphtheria-Tetanus-Pertussis Vaccine/immunology , Diphtheria-Tetanus-Pertussis Vaccine/administration & dosage , Diphtheria-Tetanus-Pertussis Vaccine/adverse effects , Australia , Vaccines, Combined/immunology , Vaccines, Combined/adverse effects , Vaccines, Combined/administration & dosage , Pertussis Vaccine/immunology , Pertussis Vaccine/adverse effects , Pertussis Vaccine/administration & dosage , Food Hypersensitivity/immunology , Food Hypersensitivity/prevention & control , Poliovirus Vaccine, Inactivated/immunology , Poliovirus Vaccine, Inactivated/adverse effects , Poliovirus Vaccine, Inactivated/administration & dosage , Haemophilus Vaccines/immunology , Haemophilus Vaccines/adverse effects , Haemophilus Vaccines/administration & dosage , Whooping Cough/prevention & control , Whooping Cough/immunology , Immunogenicity, Vaccine , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunologyABSTRACT
AIMS: To explore if intestinal immunity induced by infection with live viruses in the oral poliovirus vaccine (OPV) is essential, necessary or even helpful in interrupting transmission of wild poliovirus (WPV) for global polio eradication. METHODS: We reviewed the biology of virus-host interactions in WPV infection and its alterations by OPV-induced immunity for direct evidence of the usefulness of intestinal immunity. We also explored indirect evidence by way of the effect of the inactivated poliovirus vaccine (IPV) on the biology and on transmission dynamics of WPV. RESULTS: Immunity, systemic and intestinal, induced by infection with WPV or vaccine viruses, does not prevent re-infection with WPV or vaccine viruses respectively, when exposed. Such re-infected hosts shed virus in the throat and in faeces and are sources of further transmission. Immunity protects against polio paralysis-hence reinfection always remain asymptommatic and silent. CONCLUSION: Vaccine virus-induced intestinal immunity is not necessary for polio eradication. The continued and intensive vaccination efforts using OPV under the assumption of its superiority over IPV have resulted in the well-known undesirable effects, namely vaccine associated paralytic polio and the emergence of de-attenuated circulating vaccine-derived polioviruses, in addition to the delay in completing global WPV eradication.
Subject(s)
Disease Eradication , Immunity, Mucosal , Poliomyelitis , Poliovirus Vaccine, Oral , Poliovirus , Poliomyelitis/prevention & control , Poliomyelitis/immunology , Poliomyelitis/transmission , Humans , Poliovirus Vaccine, Oral/immunology , Poliovirus Vaccine, Oral/administration & dosage , Poliovirus/immunology , Intestinal Mucosa/immunology , Intestinal Mucosa/virology , Poliovirus Vaccine, Inactivated/immunology , Poliovirus Vaccine, Inactivated/administration & dosage , VaccinationABSTRACT
Thailand has incorporated the whole-cell (wP) pertussis vaccine into the expanded program on immunization since 1977 and has offered the acellular pertussis (aP) vaccine as an optional vaccine for infants since 2001. We followed healthy children from a clinical trial (ClinicalTrials.gov NCT02408926) in which children were randomly assigned to receive either pentavalent (DTwP-HB-Hib) or hexavalent (DTaP-IPV-HB-Hib) vaccines for their primary series (administered at 2, 4, and 6 months) and first booster vaccination (18 months). Both groups received Tdap-IPV as a second booster at the age of 4 y. Blood samples were collected for evaluation of antibody persistence to diphtheria toxoid (DT), tetanus toxoid (TT), and Bordetella pertussis (B. pertussis) between 2 and 6 y of age annually, and for the immunogenicity study of Tdap-IPV at 1 month after the second booster. Antibody persistence to Haemophilus influenzae type b (Hib) was followed until 3 y of age. A total of 105 hexavalent-vaccinated children and 91 pentavalent-vaccinated children completed this study. Both pentavalent and hexavalent groups demonstrated increased antibody levels against DT, TT, and B. pertussis antigens following the second booster with Tdap-IPV. All children achieved a seroprotective concentration for anti-DT and anti-TT IgG at 1 month post booster. The hexavalent group possessed significantly higher anti-pertactin IgG (adjusted p = .023), whereas the pentavalent group possessed significantly higher anti-pertussis toxin IgG (adjusted p < .001) after the second booster. Despite declining levels post-second booster, a greater number of children sustained protective levels of anti-DT and anti-TT IgG compared to those after the first booster.
Subject(s)
Antibodies, Bacterial , Bordetella pertussis , Diphtheria-Tetanus-Pertussis Vaccine , Haemophilus Vaccines , Haemophilus influenzae type b , Immunization, Secondary , Vaccines, Combined , Whooping Cough , Child, Preschool , Female , Humans , Infant , Male , Antibodies, Bacterial/blood , Bordetella pertussis/immunology , Diphtheria/prevention & control , Diphtheria/immunology , Diphtheria Toxoid/immunology , Diphtheria Toxoid/administration & dosage , Diphtheria-Tetanus-acellular Pertussis Vaccines/immunology , Diphtheria-Tetanus-acellular Pertussis Vaccines/administration & dosage , Diphtheria-Tetanus-Pertussis Vaccine/immunology , Diphtheria-Tetanus-Pertussis Vaccine/administration & dosage , Haemophilus Infections/prevention & control , Haemophilus Infections/immunology , Haemophilus influenzae type b/immunology , Haemophilus Vaccines/immunology , Haemophilus Vaccines/administration & dosage , Poliovirus Vaccine, Inactivated/immunology , Poliovirus Vaccine, Inactivated/administration & dosage , Tetanus Toxoid/immunology , Tetanus Toxoid/administration & dosage , Thailand , Vaccines, Combined/immunology , Vaccines, Combined/administration & dosage , Whooping Cough/prevention & control , Whooping Cough/immunology , Follow-Up StudiesABSTRACT
BACKGROUND: To assess the immunogenicity of the current primary polio vaccination schedule in China and compare it with alternative schedules using Sabin or Salk-strain IPV (sIPV, wIPV). METHODS: A cross-sectional investigation was conducted at four sites in Chongqing, China, healthy infants aged 60-89 days were conveniently recruited and divided into four groups according to their received primary polio vaccination schedules (2sIPV + bOPV, 2wIPV + bOPV, 3sIPV, and 3wIPV). The sero-protection and neutralizing antibody titers against poliovirus serotypes (type 1, 2, and 3) were compared after the last dose. RESULTS: There were 408 infants completed the protocol. The observed seropositivity was more than 96% against poliovirus types 1, 2, and 3 in all groups. IPV-only groups induced higher antibody titers(GMT) against poliovirus type 2 (Median:192, QR: 96-384, P<0.05) than the "2IPV + bOPV" group. While the "2IPV + bOPV" group induced significantly higher antibody titers against poliovirus type 1 (Median:2048, QR: 768-2048, P<0.05)and type 3 (Median:2048, QR: 512-2048, P<0.05) than the IPV-only group. CONCLUSIONS: Our findings have proved that the two doses of IPV with one dose of bOPV is currently the best polio routine immunization schedule in China.
Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , Immunization Schedule , Poliomyelitis , Poliovirus Vaccine, Inactivated , Poliovirus Vaccine, Oral , Poliovirus , Humans , Poliovirus Vaccine, Inactivated/immunology , Poliovirus Vaccine, Inactivated/administration & dosage , Poliomyelitis/prevention & control , Poliomyelitis/immunology , Infant , Poliovirus Vaccine, Oral/immunology , Poliovirus Vaccine, Oral/administration & dosage , Male , Female , Antibodies, Viral/blood , Antibodies, Viral/immunology , Cross-Sectional Studies , China , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Poliovirus/immunology , Immunogenicity, Vaccine , VaccinationABSTRACT
INTRODUCTION: Polio eradication is a current and common strategy throughout the globe. The study of the newly introduced inactivated poliovirus vaccine provides a grasp on the current status of immunization and identifies any disparities in the implementation of the vaccine throughout Ethiopia. Thus, this study aimed to demonstrate the spatial distribution, coverage, and determinants of inactivated poliovirus vaccine immunization in Ethiopia. METHOD: Spatial distribution and determinants of inactivated poliovirus vaccine immunization in Ethiopia were conducted using Ethiopian mini-demographic and health survey 2019 data. A total of 2,056 weighted children aged 12 to 35 months were included in the analysis. The association between the outcome and explanatory variables was determined by commuting the adjusted odds ratio at a 95% confidence interval. The p-value of less than 0.05 was used to declare factors as significantly associated with the inactivated poliovirus vaccine immunization. RESULT: The weighted national coverage of inactivated poliovirus vaccine immunization in Ethiopia was 51.58% at a 95% confidence interval (49.42, 53.74). While the rates of inactivated poliovirus vaccine immunization were observed to be greater in Addis Ababa, Tigiray, Amahara, and Benishangul Gumuz provinces and lower in the Somali, Afar, and SNNPR provinces of Ethiopia, Antenatal care follow-up, place of delivery, place of residence, and region were significantly associated with inactivated poliovirus immunization in Ethiopia. CONCLUSION: The distribution of inactivated poliovirus immunization was spatially variable across Ethiopia. Only about half of the children aged twelve to thirty-five months received the inactivated poliovirus vaccine in the country. The factors, both at the individual and community level, were significantly associated with inactivated poliovirus immunization. Therefore, policies and strategies could benefit from considering antenatal care follow-up, place of delivery, place of residence, and region while implementing inactivated poliovirus vaccine immunization.
Subject(s)
Poliomyelitis , Poliovirus Vaccine, Inactivated , Vaccination Coverage , Humans , Ethiopia , Poliovirus Vaccine, Inactivated/administration & dosage , Poliovirus Vaccine, Inactivated/immunology , Female , Infant , Poliomyelitis/prevention & control , Male , Child, Preschool , Vaccination Coverage/statistics & numerical data , Vaccination/statistics & numerical data , Immunization Programs , Immunization/statistics & numerical dataABSTRACT
Human enteroviruses are the most common human pathogen with over 300 distinct genotypes. Previous work with poliovirus has suggested that it is possible to generate antibody responses in humans and animals that can recognize members of multiple enterovirus species. However, cross protective immunity across multiple enteroviruses is not observed epidemiologically in humans. Here we investigated whether immunization of mice or baboons with inactivated poliovirus or enterovirus virus-like-particles (VLPs) vaccines generates antibody responses that can recognize enterovirus D68 or A71. We found that mice only generated antibodies specific for the antigen they were immunized with, and repeated immunization failed to generate cross-reactive antibody responses as measured by both ELISA and neutralization assay. Immunization of baboons with IPV failed to generate neutralizing antibody responses against enterovirus D68 or A71. These results suggest that a multivalent approach to enterovirus vaccination is necessary to protect against enterovirus disease in vulnerable populations.
Subject(s)
Antibodies, Viral , Cross Reactions , Enterovirus Infections , Poliovirus Vaccine, Inactivated , Animals , Mice , Cross Reactions/immunology , Antibodies, Viral/immunology , Enterovirus Infections/immunology , Enterovirus Infections/prevention & control , Enterovirus Infections/virology , Poliovirus Vaccine, Inactivated/immunology , Poliovirus Vaccine, Inactivated/administration & dosage , Vaccines, Virus-Like Particle/immunology , Antibodies, Neutralizing/immunology , Papio/immunology , Humans , Poliovirus/immunology , Female , Antibody Formation/immunology , Enterovirus/immunology , Mice, Inbred BALB C , Enterovirus D, Human/immunologyABSTRACT
Since the introduction of Haemophilus Influenzae type b (Hib) conjugate vaccines, invasive Hib disease has strongly declined worldwide, yet continued control of Hib disease remains important. In Europe, currently three different hexavalent combination vaccines containing Hib conjugates are marketed. In this phase IV, single-blind, randomized, controlled, multi-country study (NCT04535037), we aimed to compare, in a 2 + 1 vaccination schedule, the immunogenicity and safety and show non-inferiority, as well as superiority, of DTPa-HBV-IPV/Hib (Ih group) versus DTaP5-HB-IPV-Hib (Va group) in terms of anti-polyribosylribitol phosphate (PRP) antibody geometric mean concentrations (GMCs) and proportion of participants reaching anti-PRP antibody concentrations greater than or equal to a threshold of 5 µg/mL. One month after the booster vaccination, the anti-PRP antibody GMC ratio (Ih group/Va group) was 0.917 (95% CI: 0.710-1.185), meeting the non-inferiority criteria. The difference in percentage of participants (Ih group - Va group) reaching GMCs ≥5 µg/mL was -6.3% (95% CI: -14.1% to 1.5%), not reaching the predefined non-inferiority threshold. Interestingly, a slightly higher post-booster antibody avidity was observed in the Ih group versus the Va group. Both vaccines were well tolerated, and no safety concerns were raised. This study illustrates the different kinetics of the anti-PRP antibody response post-primary and post-booster using the two vaccines containing different Hib conjugates and indicates a potential differential impact of concomitant vaccinations on the anti-PRP responses. The clinical implications of these differences should be further studied.
Vaccination against Haemophilus influenzae type b (Hib) is included in the majority of national immunization programs worldwide and has shown to be effective in preventing Hib disease. In Europe, different vaccines containing Hib components are marketed. We compared the immune response and safety of 2 of these (DTPa-HBV-IPV/Hib, Ih group) and DTaP5-HB-IPV-Hib, Va group) in infants and toddlers, when used in a 2 + 1 schedule, i.e. two primary vaccination doses (at 2 and 4 months of age of the infant), followed by one booster dose at the age of one year. One month after the booster vaccination, the antibody concentration ratio between both groups (Ih group/Va group) was 0.917 (95% CI: 0.7101.185) showing the DTPa-HBV-IPV/Hib vaccine was non-inferior to the DTaP5-HB-IPV-Hib vaccine; the difference in percentage of participants (Ih group Va group) with antibody concentrations above 5 µg/mL was -6.3% (95% CI: −14.1% to 1.5%), which did not meet the pre-defined criterion for non-inferiority. In the Ih group, the quality of antibodies produced was somewhat higher versus the Va group. Both vaccines were well tolerated, and no safety concerns were raised. The kinetics of the immune response are different between the 2 vaccines. Since both vaccines contain different additional components (conjugated proteins), a possible effect of concomitant (simultaneously administered) vaccines was studied. Further investigations to confirm our findings are needed.
Subject(s)
Antibodies, Bacterial , Haemophilus Vaccines , Haemophilus influenzae type b , Immunization Schedule , Polysaccharides , Vaccines, Combined , Vaccines, Conjugate , Humans , Haemophilus Vaccines/immunology , Haemophilus Vaccines/adverse effects , Haemophilus Vaccines/administration & dosage , Antibodies, Bacterial/blood , Infant , Female , Male , Single-Blind Method , Vaccines, Conjugate/immunology , Vaccines, Conjugate/administration & dosage , Vaccines, Conjugate/adverse effects , Haemophilus influenzae type b/immunology , Vaccines, Combined/immunology , Vaccines, Combined/administration & dosage , Vaccines, Combined/adverse effects , Haemophilus Infections/prevention & control , Haemophilus Infections/immunology , Hepatitis B Vaccines/immunology , Hepatitis B Vaccines/administration & dosage , Hepatitis B Vaccines/adverse effects , Poliovirus Vaccine, Inactivated/immunology , Poliovirus Vaccine, Inactivated/administration & dosage , Poliovirus Vaccine, Inactivated/adverse effects , Diphtheria-Tetanus-Pertussis Vaccine/immunology , Diphtheria-Tetanus-Pertussis Vaccine/administration & dosage , Diphtheria-Tetanus-Pertussis Vaccine/adverse effects , Child, Preschool , Immunogenicity, Vaccine , EuropeABSTRACT
Delays in achieving polio eradication have led to ongoing risks of poliovirus importations that may cause outbreaks in polio-free countries. Because of the low, but non-zero risk of paralysis with oral poliovirus vaccines (OPVs), countries that achieve and maintain high national routine immunization coverage have increasingly shifted to exclusive use of inactivated poliovirus vaccine (IPV) for all preventive immunizations. However, immunization coverage within countries varies, with under-vaccinated subpopulations potentially able to sustain transmission of imported polioviruses and experience local outbreaks. Due to its cost, ease-of-use, and ability to induce mucosal immunity, using OPV as an outbreak control measure offers a more cost-effective option in countries in which OPV remains in use. However, recent polio outbreaks in IPV-only countries raise questions about whether and when IPV use for outbreak response may fail to stop poliovirus transmission and what consequences may follow from using OPV for outbreak response in these countries. We systematically reviewed the literature to identify modeling studies that explored the use of IPV for outbreak response in IPV-only countries. In addition, applying a model of the 2022 type 2 poliovirus outbreak in New York, we characterized the implications of using different OPV formulations for outbreak response instead of IPV. We also explored the hypothetical scenario of the same outbreak except for type 1 poliovirus instead of type 2. We find that using IPV for outbreak response will likely only stop outbreaks for polioviruses of relatively low transmission potential in countries with very high overall immunization coverage, seasonal transmission dynamics, and only if IPV immunization interventions reach some unvaccinated individuals. Using OPV for outbreak response in IPV-only countries poses substantial risks and challenges that require careful consideration, but may represent an option to consider for some outbreaks in some populations depending on the properties of the available vaccines and coverage attainable.
Subject(s)
Disease Outbreaks , Poliomyelitis , Poliovirus Vaccine, Inactivated , Poliovirus Vaccine, Oral , Humans , Poliomyelitis/prevention & control , Poliomyelitis/epidemiology , Poliovirus Vaccine, Inactivated/administration & dosage , Poliovirus Vaccine, Inactivated/immunology , Disease Outbreaks/prevention & control , United States/epidemiology , Poliovirus Vaccine, Oral/administration & dosage , Poliovirus Vaccine, Oral/immunology , Immunization Programs , Poliovirus/immunology , Disease Eradication/methods , Vaccination Coverage , VaccinationABSTRACT
Combining oral (OPV) and inactivated (IPV) poliovirus vaccines prevents importation of poliovirus and emergence of circulating vaccine-derived poliovirus. We measured the coverage with IPV and third dose of OPV (OPV-3) and identified determinants of coverage inequality in the most at-risk populations in Ethiopia. A national survey representing 10 partly overlapping underserved populations-pastoralists, conflict-affected areas, urban slums, hard-to-reach settings, developing regions, newly formed regions, internally displaced people (IDPs), refugees, and districts neighboring international and interregional boundaries-was conducted among children 12 to 35 months old (N = 3,646). Socioeconomic inequality was measured using the concentration index (CIX) and decomposed using a regression-based approach. One-third (95% CI: 31.5-34.0%) of the children received OPV-3 and IPV. The dual coverage was below 50% in developing regions (19.2%), pastoralists (22.0%), IDPs (22.3%), districts neighboring international (24.1%) and interregional (33.3%) boundaries, refugees (27.0%), conflict-affected areas (29.3%), newly formed regions (33.5%), and hard-to-reach areas (38.9%). Conversely, coverage was better in urban slums (78%). Children from poorest households, living in villages that do not have health posts, and having limited health facility access had increased odds of not receiving the vaccines. Low paternal education, dissatisfaction with vaccination service, fear of vaccine side effects, living in female-headed households, having employed and less empowered mothers were also risk factors. IPV-OPV3 coverage favored the rich (CIX = -0.161, P < 0.001), and causes of inequality were: inaccessibility of health facilities (13.3%), dissatisfaction with vaccination service (12.8%), and maternal (4.9%) and paternal (4.9%) illiteracy. Polio vaccination coverage in the most at-risk populations in Ethiopia is suboptimal, threatening the polio eradication initiative.
Subject(s)
Poliomyelitis , Poliovirus Vaccine, Inactivated , Poliovirus Vaccine, Oral , Child, Preschool , Humans , Infant , Ethiopia , Poliomyelitis/prevention & control , Poliovirus Vaccine, Inactivated/administration & dosage , Poliovirus Vaccine, Oral/administration & dosage , Risk Factors , Vaccination/statistics & numerical dataABSTRACT
BACKGROUND: This study investigated the immunogenicity and safety of a fully liquid, hexavalent, diphtheria (D)-tetanus (T)-whole-cell pertussis (wP)-inactivated poliovirus (IPV)-hepatitis B (HB)- Haemophilus influenzae b (PRP-T) vaccine compared to licensed DTwP-HB-PRP~T, IPV, and bivalent oral poliovirus (bOPV) vaccines following co-administration with other pediatric vaccines [pneumococcal conjugate vaccine (PCV13) and rotavirus vaccine]. METHODS: Phase III, randomized, open-label study in Thailand. Healthy infants received DTwP-IPV-HB-PRP~T at 2, 4 and 6 months of age (N = 228), or DTwP-HB-PRP~T and bOPV (2, 4 and 6 months of age) and IPV (4 months of age) (N = 231). All participants received PCV13 (2, 4 and 6 months of age) and rotavirus vaccine (2 and 4 months of age). Immunogenicity for all antigens was assessed using validated assays, and noninferiority post-third dose was evaluated for anti-D, anti-T, anti-pertussis [anti-pertussis toxin (anti-PT) and anti-fimbriae 2/3 (anti-FIM)], anti-polio 1, 2, 3, anti-HB, and anti-PRP~T. Safety was assessed using parental reports. RESULTS: Noninferiority was demonstrated for each antigen, and overall noninferiority of DTwP-IPV-HB-PRP~T versus DTwP-HB-PRP~T+bOPV+IPV was concluded. Similarity in each group was observed for the GMC ratio for antirotavirus antibodies (20.9 and 17.3, respectively) and anti-PCV13 antibodies (range: 8.46-32.6 and 7.53-33.1, respectively). Two serious adverse events were related to DTwP-IPV-HB-PRP~T (febrile convulsion and acute febrile illness) and 1 was related to DTwP-HB-PRP~T+bOPV+IPV (febrile seizure), but overall there were no safety concerns with similar rates of participants experiencing solicited (99.1% and 98.3%) and unsolicited (19.3% and 19.5%) adverse events in each group. CONCLUSIONS: This study confirmed the suitability of DTwP-IPV-HB-PRP~T primary series vaccination in combination with rotavirus and PCV13 vaccines.
Subject(s)
Diphtheria-Tetanus-Pertussis Vaccine , Haemophilus Vaccines , Hepatitis B Vaccines , Poliovirus Vaccine, Inactivated , Rotavirus Vaccines , Vaccines, Combined , Humans , Infant , Antibodies, Bacterial , Antibodies, Viral , Diphtheria-Tetanus-Pertussis Vaccine/administration & dosage , Diphtheria-Tetanus-Pertussis Vaccine/immunology , Haemophilus Vaccines/administration & dosage , Haemophilus Vaccines/immunology , Hepatitis B , Hepatitis B Vaccines/administration & dosage , Hepatitis B Vaccines/immunology , Immunization Schedule , Poliovirus Vaccine, Inactivated/administration & dosage , Poliovirus Vaccine, Inactivated/immunology , Rotavirus Vaccines/administration & dosage , Rotavirus Vaccines/immunology , Thailand , Vaccines, Combined/administration & dosage , Vaccines, Combined/immunology , Vaccines, Conjugate/administration & dosage , Vaccines, Conjugate/immunology , Pneumococcal Vaccines/administration & dosage , Pneumococcal Vaccines/immunology , Immunogenicity, VaccineABSTRACT
An antenatal pertussis vaccination programme was introduced in 2012 in the UK in the context of a national outbreak of pertussis. It has been shown that a lower antibody response to primary immunisation can be seen for certain pertussis antigens in infants born to women who received pertussis-containing antenatal vaccines, a phenomenon known as blunting. The longer-term impact of this has not been documented previously, and accordingly was evaluated in this study. Children were predominantly recruited from a previous study in which their mothers had received acellular pertussis-containing antenatal vaccines (dTaP3-IPV [diphtheria toxoid, tetanus toxoid, three antigen acellular pertussis and inactivated polio] or dTaP5-IPV [diphtheria toxoid, tetanus toxoid, five antigen acellular pertussis and inactivated polio]), or no pertussis-containing vaccine. Blood samples were obtained prior to and one month after the acellular pertussis-containing preschool booster (dTaP5-IPV) was given at around age 3 years 4 months. Pre- and post-booster immunoglobulin G (IgG) geometric mean concentrations (GMCs) against pertussis toxin, filamentous haemagglutinin, fimbriae 2 & 3, and pertactin, were compared. Prior to the receipt of the preschool booster, there was no difference in the IgG GMCs against pertussis-specific antigens between children born to women vaccinated with dTaP3-IPV and dTaP5-IPV; however, IgG GMCs against pertussis toxin were significantly lower in children born to women vaccinated with dTaP3-IPV compared with children born to unvaccinated women (geometric mean ratio 0.42 [95 % CI 0.22-0.78], p = 0.03). One month after the receipt of the preschool booster there was no differences between the groups. The blunting effect of antenatal pertussis vaccine on pertussis responses in children can persist until preschool age, although it is overcome by the administration of a booster dose. ClinicalTrials.gov registration number: NCT03578120.
Subject(s)
Diphtheria-Tetanus-acellular Pertussis Vaccines , Immunization, Secondary , Poliovirus Vaccine, Inactivated , Child, Preschool , Female , Humans , Infant , Pregnancy , Antibodies, Bacterial/blood , Diphtheria-Tetanus-acellular Pertussis Vaccines/administration & dosage , Immunoglobulin G/blood , Poliomyelitis/prevention & control , Poliovirus Vaccine, Inactivated/administration & dosage , Vaccines, Combined/administration & dosage , Whooping Cough/prevention & controlABSTRACT
Ante el riesgo real de ocurrencia de brotes de parálisis fláccida aguda en la región debidos a poliovirus derivado de la vacuna Sabin o a la importación de poliovirus salvaje, la Sociedad Latinoamericana de Infectología Pediátrica comisionó a un grupo ad hoc de expertos integrantes del Comité de Vacunas y Biológicos de la institución, para redactar un documento oficial de posición sobre la necesidad imperiosa de incrementar los niveles de inmunización contra la enfermedad en la región e incorporar definitivamente en forma exclusiva la vacuna de polio inactivada en todos los esquemas nacionales de vacunación. La presente publicación discute las principales conclusiones y recomendaciones generadas como resultado de esta actividad.
Given the actual risk of poliomyelitis outbreaks in the region due to poliovirus derived from the Sabin vaccine or the importation of wild poliovirus, the Latin American Society of Pediatric Infectious Diseases commissioned an ad hoc group of experts from the institution's Vaccines and Biologicals Committee, to draft an official position paper on the urgent need to increase immunization levels against the disease in the region and incorporate inactivated polio vaccine exclusive schedules in all national immunization programs. This publication discusses the main conclusions and recommendations generated as a result of such activity.
Subject(s)
Humans , Poliomyelitis/prevention & control , Poliovirus Vaccine, Inactivated/administration & dosage , Poliovirus Vaccine, Inactivated/supply & distribution , Poliovirus Vaccine, Oral/administration & dosage , Poliovirus Vaccine, Oral/supply & distribution , Paralysis/etiology , Poliomyelitis/complications , Poliomyelitis/epidemiology , Poliovirus/immunology , Vaccination Coverage , Disease Eradication , Epidemiological Monitoring , Latin AmericaABSTRACT
Given the actual risk of poliomyelitis outbreaks in the region due to poliovirus derived from the Sabin vaccine or the importation of wild poliovirus, the Latin American Society of Pediatric Infectious Diseases commissioned an ad hoc group of experts from the institution's Vaccines and Biologicals Committee, to draft an official position paper on the urgent need to increase immunization levels against the disease in the region and incorporate inactivated polio vaccine exclusive schedules in all national immunization programs. This publication discusses the main conclusions and recommendations generated as a result of such activity.
Ante el riesgo real de ocurrencia de brotes de parálisis fláccida aguda en la región debidos a poliovirus derivado de la vacuna Sabin o a la importación de poliovirus salvaje, la Sociedad Latinoamericana de Infectología Pediátrica comisionó a un grupo ad hoc de expertos integrantes del Comité de Vacunas y Biológicos de la institución, para redactar un documento oficial de posición sobre la necesidad imperiosa de incrementar los niveles de inmunización contra la enfermedad en la región e incorporar definitivamente en forma exclusiva la vacuna de polio inactivada en todos los esquemas nacionales de vacunación. La presente publicación discute las principales conclusiones y recomendaciones generadas como resultado de esta actividad.
Subject(s)
Humans , Poliomyelitis/prevention & control , Poliovirus Vaccine, Inactivated/administration & dosage , Poliovirus Vaccine, Inactivated/supply & distribution , Poliovirus Vaccine, Oral/administration & dosage , Poliovirus Vaccine, Oral/supply & distribution , Paralysis/etiology , Poliomyelitis/complications , Poliomyelitis/epidemiology , Poliovirus/immunology , Vaccination Coverage , Disease Eradication , Epidemiological Monitoring , Latin AmericaABSTRACT
OBJECTIVE: To assess the contribution of partners in the introduction of two new vaccines concurrently: pneumococcal 10-valent conjugate vaccine (PCV-10) and inactivated polio vaccine (IPV) into the routine Expanded Programme on Immunization (EPI) in Bangladesh. DESIGN: We conducted a prospective process evaluation that included the theory of change development, root cause analysis and in-depth investigation. As part of process tracking, we reviewed relevant documents, observed trainers' and vaccinators' training and key stakeholder meetings. We analysed the data thematically. SETTING: We purposively selected eight Upazila (subdistrict) and one city corporation covering nine districts and seven administrative divisions of Bangladesh. PARTICIPANTS: Nineteen national key informants were interviewed and 16 frontline health workers were invited to the group discussions considering their involvement in the vaccine introduction process. RESULTS: The EPI experienced several challenges during the joint introduction of PCV-10 and IPV, such as frequent changes in the vaccine introduction schedule, delays in budget allocation, vaccine supply shortage and higher wastage rates of IPV. EPI addressed these challenges in collaboration with its partners, that is, the World Health Organization (WHO) and United Nations Children's Fund (UNICEF), who provided technical assistance to develop a training curriculum and communication materials and enhanced demand generation at the community level. In addition, the WHO conducted a country readiness assessment for PCV-10, and UNICEF supported vaccine shipment. Other government ministries, City Corporations and municipalities also supported the EPI. CONCLUSIONS: The partnership among the EPI stakeholders effectively addressed various operational challenges during the joint introduction of PCV-10 and IPV helped strengthen Bangladesh's immunisation systems. These accomplishments are attributed to several factors that should be supported and strengthened for future vaccine introductions in Bangladesh and other low and-middle countries.
Subject(s)
Immunization Programs , Pneumococcal Vaccines , Poliovirus Vaccine, Inactivated , Bangladesh , Child , Humans , Immunization Programs/organization & administration , Pneumococcal Vaccines/administration & dosage , Poliovirus Vaccine, Inactivated/administration & dosage , Program Evaluation , Prospective Studies , Vaccines, ConjugateABSTRACT
BACKGROUND: A rapid increase in circulating vaccine-derived poliovirus type 2 outbreaks, and the need to reserve inactivated poliovirus vaccine (IPV) for routine immunisation, has increased the value of fractional dose IPV (fIPV) as a measure to prevent acute flaccid paralysis. However, the intradermal route of administration has been viewed as prohibitive to outbreak response campaigns. We aimed to establish the immunogenicity and safety of administering intradermal fIPV with a disposable syringe jet injector (DSJI) or an intradermal adaptor (IDA) compared with standard administration with a BCG needle and syringe (N&S). METHODS: This pragmatic, non-inferiority trial was undertaken in a campaign setting in communities in The Gambia. Children aged 4-59 months without contraindication to vaccination were eligible. Children were not individually randomly assigned; instead, the vaccination teams were randomly assigned (1:1:1) to one of three administration methods. Parents and the field team were not masked, but laboratory personnel were masked. Baseline demographic and anthropometric data were collected from the participants. Public health officers experienced at intradermal immunisation, and nurses without experience, had 2 h of training on each of the administration methods before the campaign. Participants were vaccinated using the administration method in use by the vaccination team in their community. Poliovirus serum neutralising antibodies (SNA) were measured in children aged 24-59 months before and 4 weeks after vaccination. Adverse events and data on injection quality were collected from all participants. The primary outcome was the type 2 immune response rate (seroconversion in seronegative [SNA titre <8] children plus a 4-fold titre rise in seropositive children). Adjusted differences in the immune response between the DSJI or IDA group versus the N&S group were calculated with 97·5% CIs. A margin of -10% was used to define the non-inferiority of DSJI or IDA compared to N&S. Immunogenicity analysis was done per protocol. The trial is registered with ClinicalTrials.govNCT02967783 and has been completed. FINDINGS: Between Oct 28 and Dec 29, 2016, 3189 children aged 4-59 months were recruited, of whom 3170 were eligible. Over 3 days, 2720 children were vaccinated (N&S, 917; IDA, 874; and DSJI, 929). Among 992 children aged 25-59 months with a baseline SNA available, 90·1% (95% CI 86·1-92·9; 281/312) of those vaccinated using the DSJI had an immune response to type 2 compared with 93·8% (90·6-95·8; 331/353) of those vaccinated with N&S and 96·6% (94·0-98·0; 316/327) of those vaccinated with IDA. All (53/53) type 2 seronegative children seroconverted. For polio type 2, non-inferiority was shown for both the IDA (adjusted difference 0·7% [97·5% CI -3·3 to 4·7], unadjusted difference 2·9% [-0·9 to 6·8]) and DSJI (adjusted difference -3·3% [-8·3 to 1·5], unadjusted difference -3·7% [-8·7 to 1·1]) compared with N&S. Non-inferiority was shown for type 1 and 3 for the IDA and DSJI. Neither injection quality nor the training and experience of the vaccinators had an effect on immune response. No safety concerns were reported. INTERPRETATION: In a campaign, intradermal fIPV is safe and generates consistent immune responses that are not dependent on vaccinator experience or injection quality when administered using an N&S, DSJI, or IDA. Countries facing vaccine-derived poliovirus type 2 outbreaks should consider fIPV campaigns to boost population immunity and prevent cases of acute flaccid paralysis. FUNDING: World Health Organization and the Medical Research Council.
Subject(s)
Poliomyelitis/prevention & control , Poliovirus Vaccine, Inactivated/administration & dosage , Poliovirus Vaccine, Inactivated/immunology , Child, Preschool , Dose-Response Relationship, Drug , Equivalence Trials as Topic , Female , Gambia , Humans , Infant , Injections, Intradermal , MaleABSTRACT
BACKGROUND: Since WHO recommended introduction of at least a single dose of inactivated poliovirus vaccine (IPV) in routine immunisation schedules, there have been global IPV shortages. Fractional-dose IPV (fIPV) administration is one of the strategies to ensure IPV availability. We reviewed studies comparing the effects of fractional with full-dose IPV vaccination to determine when seroconversion proportions with each strategy become similar in children aged 5 years and younger. METHOD: In this systematic review and meta-analysis, we searched 16 databases in July, 2019, for trials and observational studies, including ongoing studies that compare immunogenicity and adverse events of fractional-dose (0·1 mL) to full-dose (0·5 mL) IPV in healthy children aged 5 years or younger regardless of study design, number of doses, and route of administration. Screening, selection of articles, data extraction, and risk of bias assessment were done in duplicate, and conflicts were resolved by discussion or arbitration by a third author. We assessed immunogenicity, the main outcome, as proportion of seroconverted participants and changes in geometric mean titres of anti-poliovirus antibodies. Timepoints were eligible for analysis if measurements were done at least 4 weeks after vaccination. Summary estimates were pooled by use of random-effects meta-analysis. Analysis was stratified by study design, type of outcome measure, type of poliovirus, and number of doses given. We assessed heterogeneity using the χ2 test of homogeneity and quantified it using the I2 statistic. We assessed risk of bias using the Cochrane risk of bias tool, and the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. The study is registered with PROSPERO, CRD42018092647. FINDINGS: 860 records were screened for eligibility, of which 36 potentially eligible full-text articles were assessed and 14 articles were included in the final analysis: two ongoing trials and 12 articles reporting on ten completed studies. For poliovirus type 2, there were no significant differences in the proportions of seroconversions between fractional and full doses of IPV for two or three doses: the risk ratio for serconversion at one dose was 0·61 (95% CI 0·51-0·72), at two doses was 0·90 (0·82-1·00), and at three doses was 0·95 (0·91-1·00). Geometric mean titres (GMTs) for poliovirus type 2 were lower for fIPV than for full-dose IPV: -0·51 (95% CI -0·87 to -0·14) at one dose, -0·49 (-0·70 to -0·28) at two doses, and -0·98 (-1·46 to -0·51) at three doses. The seroconversion meta-analysis for the three-dose comparison was homogeneous (p=0·45; I2=0%), whereas heterogeneity was observed in the two-dose (p<0·00001; I2=88%) and one-dose (p=0·0004; I2=74%) comparisons. Heterogeneity was observed in meta-analyses of GMTs for one-dose (p<0·00001; I2=92%), two-dose (p=0·002; I2=80%), and three-dose (p<0·00001; I2=93%) comparisons. Findings for types 1 and 3 were similar to those for type 2. The certainty of the evidence was high for the three-dose comparisons and moderate for the rest of the comparisons. INTERPRETATION: There is no substantial difference in seroconversion between three doses of fIPV and three doses of full-dose IPV, although the full dose gives higher titres of antibodies for poliovirus type 1, 2, and 3. Use of fractional IPV instead of the full dose can stretch supplies and possibly lower the cost of vaccination. FUNDING: South African Medical Research Council and the National Research Foundation of South Africa.