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Objectives: The National Immunization Program allows using a different manufacturer's vaccine for follow-up doses when the same vaccine is unavailable. This study aimed to evaluate the safety and immunogenicity of administering a third dose of Sabin strain (sIPV) from a different manufacturer in infants who had previously received two doses of sIPV. Methods: This randomized, blinded, controlled trial enrolled 200 healthy infants (≤12 months) to assess the safety and immunogenicity of sequential vaccination, who were randomly assigned to receive a third dose of sIPV from either a different manufacturer (experimental group) or the same manufacturer as the first two doses (control group). The study took place in Xiaogan City, Hubei Province, China, from 20 May 2024 to 6 September 2024. Immunogenicity and safety were assessed using per-protocol and safety populations, respectively. Results: The seroconversion rates for poliovirus types 1, 2, and 3 were 79.52 %, 67.47 %, and 74.70 % in the experimental group, respectively, compared to 73.56 %, 49.43 %, and 63.22 % in the control group, with P-values of 0.360, 0.017, and 0.106, respectively. The most common systemic adverse event (AE) was fever, and no significant differences in the incidence of AEs between the two groups were observed. No serious adverse events related to vaccines were reported. Conclusion: Sequential vaccination with sIPV from different manufacturers demonstrated superior immunogenicity compared to the initial vaccine, with no significant safety differences, indicating that using vaccines from different manufacturers for sequential dosing is a feasible and effective option.

Replacing oral polio vaccines with inactivated polio vaccines (IPVs) is necessary to stop the potential transmission of vaccine-derived polio viruses. We aimed to compare the safety and immunogenicity of a dose-sparing IPV (ds-IPV) with a full-dose IPV in infants in Bangladesh. This double-blind, randomised, controlled, phase 3 study was done at two field sites in Bangladesh (Kamlapur and Matlab). Eligible participants were healthy infants aged 6–8 weeks, with parents who intended to reside in the area during the study period. Participants were randomly assigned (1:1:1:1) to receive either ds-IPV from one of the three lots (lot A, B, or C; Serum Institute of India, Pune, India) or an IPV (Serum Institute of India). Three intramuscular doses (0·5 mL) were administered at age 6, 10, and 14 weeks in addition to other standard vaccines. The study staff involved in safety evaluation, study procedures, parents of the participants, and the laboratory personnel were masked to the treatment allocations. The primary endpoint was seroconversion for poliovirus types 1, 2, and 3 at 28 days after the third dose, assessed in the per-protocol and full analysis populations. Solicited adverse events were collected up to 4 days after each vaccine dose and unsolicited adverse events and serious adverse events were collected up to 28 days after the third dose. This study is registered with ClinicalTrials.gov, NCT05163561, and is complete. Between Jan 9, 2022, and April 29, 2023, 1072 eligible participants were randomly assigned to receive ds-IPV (n=801) or IPV (n=267), of whom 1052 completed the study. 755 (96% [95% CI 94 to 97]) of 786 participants in the ds-IPV group versus 256 (97% [94 to 98]) of 265 participants in the IPV group had seroconversion for poliovirus type 1 (difference –0·55% [95% CI –3·05 to 1·95]). 744 (95% [93 to 96]) of 786 participants in the ds-IPV group versus 261 (98% [96 to 100]) of 265 participants in the IPV group had seroconversion for poliovirus type 2 (difference –3·83% [–6·48 to –1·19]). 765 (97% [96 to 98]) of 786 participants in the ds-IPV group versus 260 (98% [96 to 99]) of 265 participants in the IPV group had seroconversion for poliovirus type 3 (difference –0·78% [–2·73 to 1·16]). Solicited events were observed in 446 (56%) of 801 participants in the ds-IPV group and 143 (54%) of 267 participants in the IPV group. Unsolicited events were observed in 746 (93%) of 801 participants in the ds-IPV group and 250 (94%) of 267 participants in the IPV group. Serious adverse events were observed in 23 (3%) of 801 participants in the ds-IPV group and five (2%) of 267 participants in the IPV group. The common serious adverse events were pneumonia (n=10 in the ds-IPV group; n=3 in the IPV group), bronchiolitis (n=3 in the ds-IPV group; n=1 in the IPV group), and diarrhoea (n=3 in the ds-IPV group; n=1 in the IPV group). None of the unsolicited events and serious adverse events were causally related to the study vaccines. Delivery of three intramuscular doses of the novel ds-IPV vaccine is safe and immunologically non-inferior to the delivery of three intramuscular doses of IPV, and the dose sparing formulation might therefore become an attractive option for some national immunisation programmes due to lower expected vaccine costs. Serum Institute of India.

Following the global eradication of wild poliovirus, countries using live attenuated oral poliovirus vaccines will transition to exclusive use of inactivated poliovirus vaccine (IPV) or fractional doses of IPV (f-IPV; a f-IPV dose is one-fifth of a normal IPV dose), but IPV supply and cost constraints will necessitate dose-sparing strategies. We compared immunisation schedules of f-IPV and IPV to inform the choice of optimal post-eradication schedule. This randomised open-label, multicentre, phase 3, non-inferiority trial was done at two centres in Panama and one in the Dominican Republic. Eligible participants were healthy 6-week-old infants with no signs of febrile illness or known allergy to vaccine components. Infants were randomly assigned (1:1:1:1, 1:1:1:2, 2:1:1:1), using computer-generated blocks of four or five until the groups were full, to one of four groups and received: two doses of intradermal f-IPV (administered at 14 and 36 weeks; two f-IPV group); or three doses of intradermal f-IPV (administered at 10, 14, and 36 weeks; three f-IPV group); or two doses of intramuscular IPV (administered at 14 and 36 weeks; two IPV group); or three doses of intramuscular IPV (administered at 10, 14, and 36 weeks; three IPV group). The primary outcome was seroconversion rates based on neutralising antibodies for poliovirus type 1 and type 2 at baseline and at 40 weeks (4 weeks after the second or third vaccinations) in the per-protocol population to allow non-inferiority and eventually superiority comparisons between vaccines and regimens. Three co-primary outcomes concerning poliovirus types 1 and 2 were to determine if seroconversion rates at 40 weeks of age after a two-dose regimen (administered at weeks 14 and 36) of intradermally administered f-IPV were non-inferior to a corresponding two-dose regimen of intramuscular IPV; if seroconversion rates at 40 weeks of age after a two-dose IPV regimen (weeks 14 and 36) were non-inferior to those after a three-dose IPV regimen (weeks 10, 14, and 36); and if seroconversion rates after a two-dose f-IPV regimen (weeks 14 and 36) were non-inferior to those after a three-dose f-IPV regimen (weeks 10, 14, and 36). The non-inferiority boundary was set at −10% for the lower bound of the two-sided 95% CI for the seroconversion rate difference.. Safety was assessed as serious adverse events and important medical events. This study is registered on ClinicalTrials.gov, NCT03239496. From Oct 23, 2017, to Nov 13, 2018, we enrolled 773 infants (372 [48%] girls) in Panama and the Dominican Republic (two f-IPV group n=217, three f-IPV group n=178, two IPV group n=178, and three IPV group n=200). 686 infants received all scheduled vaccine doses and were included in the per-protocol analysis. We observed non-inferiority for poliovirus type 1 seroconversion rate at 40 weeks for the two f-IPV dose schedule (95·9% [95% CI 92·0–98·2]) versus the two IPV dose schedule (98·7% [95·4–99·8]), and for the three f-IPV dose schedule (98·8% [95·6–99·8]) versus the three IPV dose schedule (100% [97·9–100]). Similarly, poliovirus type 2 seroconversion rate at 40 weeks for the two f-IPV dose schedule (97·9% [94·8–99·4]) versus the two IPV dose schedule (99·4% [96·4–100]), and for the three f-IPV dose schedule (100% [97·7–100]) versus the three IPV dose schedule (100% [97·9–100]) were non-inferior. Seroconversion rate for the two f-IPV regimen was statistically superior 4 weeks after the last vaccine dose in the 14 and 36 week schedule (95·9% [92·0–98·2]) compared with the 10 and 14 week schedule (83·2% [76·5–88·6]; p=0·0062) for poliovirus type 1. Statistical superiority of the 14 and 36 week schedule was also found for poliovirus type 2 (14 and 36 week schedule 97·9% [94·8–99·4] vs 10 and 14 week schedule 83·9% [77·2–89·2]; p=0·0062), and poliovirus type 3 (14 and 36 week schedule 84·5% [78·7–89·3] vs 10 and 14 week schedule 73·3% [65·8–79·9]; p=0·0062). For IPV, a two dose regimen administered at 14 and 36 weeks (99·4% [96·4–100]) was superior a 10 and 14 week schedule (88·9% [83·4–93·1]; p<0·0001) for poliovirus type 2, but not for type 1 (14 and 36 week schedule 98·7% [95·4–99·8] vs 10 and 14 week schedule 95·6% [91·4–98·1]), or type 3 (14 and 36 week schedule 97·4% [93·5–99·3] vs 10 and 14 week schedule 93·9% [89·3–96·9]). There were no related serious adverse events or important medical events reported in any group showing safety was unaffected by administration route or schedule. Our observations suggest that adequate immunity against poliovirus type 1 and type 2 is provided by two doses of either IPV or f-IPV at 14 and 36 weeks of age, and broad immunity is provided with three doses of f-IPV, enabling substantial savings in cost and supply. These novel clinical data will inform global polio immunisation policy for the post-eradication era. Bill & Melinda Gates Foundation.

To evaluate the immunogencity and safety for three immunization schedules of inactivated poliovirus vaccine (IPV) and bivalent oral poliovirus vaccine (bOPV) for providing a basis for further optimization of the polio sequential immunization schedule. To obtain immunogenicity data and to active surveillance the occurrence of adverse events following immunization (AEFI), healthy infants ≥ 2 months of age were randomly chosen in Hebei Province, and were divided into three groups to be vaccinated with IPV-bOPV-bOPV(Group a), IPV-IPV-bOPV(Group b) and IPV-IPV-IPV(Group c) at 2, 3 and 4 months of age respectively. AEFI cases related to poliomyelitis vaccines in Hebei province by passive surveillance from January 1, 2018 to December 31, 2022 were obtained from national adverse event following immunization surveillance system (NAEFISS). After basic immunization with polio vaccine, the positive conversion rate of neutralizing antibodies of types I, II and III were all > 97.00% and the positive rates were all > 98.00%, the geometric mean titer (GMT) was significantly higher than that before basic immunization, the GMT level of neutralizing poliovirus antibody after basic immunization was the highest in type I, followed by type III, and the lowest in type II. A total of 16 AEFI cases (2.52%) were reported by active surveillance, and 2903 AEFI cases (1.40%) were reported by passive surveillance. AEFI reported by both monitoring modalities were dominated by fever of common vaccine reactions. No rare serious adverse reactions like VAPP etc. were monitored and the overall regression was positive. All three immunization schedules for polio vaccine have demonstrated good immunogenicity and safety when administered to healthy populations.

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.

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. 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). 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 registered at the Australian and New Zealand Clinical 207 Trial Registry (ACTRN12617000065392p).

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. We did a randomised, 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 randomly 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 randomisation 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 ClinicalTrials.gov, number NCT01841671, and is closed to new participants. 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 resulted 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). 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. Bill & Melinda Gates Foundation.

Combination vaccines are effective in simplifying complex vaccination schedules involving multiple vaccines. A fully liquid hexavalent diphtheria (D)-tetanus (T)-whole-cell pertussis (wP)- hepatitis B (HepB)-inactivated poliovirus (IPV)-Haemophilus influenzae b (Hib) vaccine (HEXASIIL®), manufactured by Serum Institute of India Pvt. Ltd. was tested for safety and immunogenicity following booster vaccination. This was a phase-II/III, open label, multicentric, controlled trial in toddlers (phase II) and infants (phase III) in India. This manuscript presents results of phase II. Healthy toddlers aged 12–24 months were randomized (1:1) to receive a 0.5 ml booster dose of HEXASIIL® or comparator Pentavac SD + Poliovac, intramuscularly and followed for 28 days for safety assessment. Blood samples were collected pre-vaccination and 28 days post-vaccination to assess immunogenicity. Descriptive summary statistics were provided for safety and immunogenecity analyses. A total of 223 subjects were randomized. One subject droped out prior to dosing, due to consent withdrawal. Thus, 222 subjects received study vaccine (110 HEXASIIL® and 112 comparator). Frequency of solicited adverse events was comparable between HEXASIIL® and comparator (85.5 % vs 90.2 %). Most local and systemic solicited AEs were mild to moderate in severity. All events resolved completely without any sequelae and none led to subject discontinuation. No vaccine related serious AE was reported. Post vaccination, seroprotection rates against tetanus, Hib and polio type 1 and 3 were 100 % in both the groups. Seroprotection rates for diphtheria (99.1 % vs 100 %) and polio type 2 (98.2 % vs 100 %) were observed in HEXASIIL® and comparator group, respectively. For Hepatitis B, seroprotection was >99 % in both groups. Seroconversion observed for Bordetella Pertussis (94.5 % vs 95.4 %) and Pertussis Toxin (77.1 % vs 87.2 %) in HEXASIIL® and comparator group, respectively. HEXASIIL® vaccine was found to be safe and immunogenic in toddlers and supported its further clinical development in infants. Clinical Trial Registration – CTRI/2019/11/022052. •Combination vaccines simplify vaccination schedules and improve compliance.•HEXASIIL® vaccine was compared to licensed DTwP-HepB-Hib + IPV vaccines.•HEXASIIL® had good safety and immunogenicity profile.•The data supported further evaluation of HEXASIIL® in infants.

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. 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. 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%. 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.

Polio eradication needs a new routine immunisation schedule—three or four doses of bivalent type 1 and type 3 oral poliovirus vaccine (bOPV) and one dose of inactivated poliovirus vaccine (IPV), but no immunogenicity data are available for this schedule. We aimed to assess immunogenicity of this vaccine schedule. We did an open-label, randomised controlled trial in four centres in India. After informed consent was obtained from a parent or legally acceptable representative, healthy newborn babies were randomly allocated to one of five groups: trivalent OPV (tOPV); tOPV plus IPV; bOPV; bOPV plus IPV; or bOPV plus two doses of IPV (2IPV). The key eligibility criteria were: full-term birth (≥37 weeks of gestation); birthweight ≥2·5 kg; and Apgar score of 9 or more. OPV was administered at birth, 6 weeks, 10 weeks, and 14 weeks; IPV was administered intramuscularly at 14 weeks. The primary study objective was to investigate immunogenicity of the new vaccine schedule, assessed by seroconversion against poliovirus types 1, 2, and 3 between birth and 18 weeks in the per-protocol population (all participants with valid serology results on cord blood and at 18 weeks). Neutralisation assays tested cord blood and sera collected at 14 weeks, 18 weeks, 19 weeks, and 22 weeks by investigators masked to group allocation. This trial was registered with the India Clinical Trials Registry, number CTRI/2013/06/003722. Of 900 newborn babies enrolled between June 13 and Aug 29, 2013, 782 (87%) completed the per-protocol requirements. Between birth and age 18 weeks, seroconversion against poliovirus type 1 in the tOPV group occurred in 162 of 163 (99·4%, 95% CI 96·6–100), in 150 (98·0%, 94·4–99·6) of 153 in the tOPV plus IPV group, in 153 (98·7%, 95·4–99·8) of 155 in the bOPV group, in 155 (99·4%, 96·5–100) of 156 in the bOPV plus IPV group, and in 154 (99·4%, 96·5–100) of 155 in the bOPV plus 2IPV group. Seroconversion against poliovirus type 2 occurred in 157 (96·3%, 92·2–98·6) of 163 in the tOPV group, 153 (100%, 97·6–100·0) of 153 in the tOPV plus IPV group, 29 (18·7%, 12·9–25·7) of 155 in the bOPV group, 107 (68·6%, 60·7–75·8) of 156 in the bOPV plus IPV group, and in 121 (78·1%, 70·7–84·3) of 155 in the bOPV plus 2IPV group. Seroconversion against poliovirus type 3 was achieved in 147 (90·2%, 84·5–94·3) of 163 in the tOPV group, 152 (99·3%, 96·4–100) of 153 in the tOPV plus IPV group, 151 (97·4%, 93·5–99·3) of 155 in the bOPV group, 155 (99·4%, 96·5–100) of 156 in the bOPV plus IPV group, and 153 (98·7%, 95·4–99·8) of 155 in the bOPV plus 2IPV group. Superiority was achieved for vaccine regimens including IPV against poliovirus type 3 compared with those not including IPV (tOPV plus IPV vs tOPV alone, p=0·0008; and bOPV plus IPV vs bOPV alone, p=0·0153). 12 serious adverse events occurred (six in the tOPV group, one in the tOPV plus IPV group, three in the bOPV group, zero in the bOPV plus IPV group, and two in the bOPV plus 2IPV group), none of which was attributed to the trial intervention. The new vaccination schedule improves immunogenicity against polioviruses, especially against poliovirus type 3. WHO, through a grant from Rotary International (grant number 59735).