Immunogenicity and safety of a dose-sparing inactivated poliovirus vaccine in infants in India: a phase 2/3, double-blind, randomised controlled trial

BACKGROUND: Several countries are using fractionated or limited-dose regimens of full dose inactivated polio vaccine (IPV) in infants in addition to oral poliovirus vaccine (OPV), due to procurement cost of IPV and delivery challenges for its campaign use. An adjuvanted dose-sparing IPV (ds-IPV) with around a one-fourth antigen content of the full dose of IPV was developed in India. A non-inferiority trial was conducted to compare the immune response of ds-IPV with IPV in infants. METHODS: A phase 2/3, double-blind, randomised controlled trial was conducted at nine tertiary care hospitals in India. Healthy infants aged 6-8 weeks, who received a birth dose of bivalent OPV were enrolled. Participants with fever or acute infection, and previous receipt or plan to receive any other poliovirus-containing vaccines were excluded. Infants were randomly assigned (1:1; block randomisation managed through an interactive web response system) to receive either ds-IPV or IPV in a three-dose regimen-a single dose of 0·5 mL administered by intramuscular route at age 6 weeks, 10 weeks, and 14 weeks. The vaccine syringes were masked with an opaque peel before administration to maintain masking. All participants were concomitantly administered oral rotavirus vaccine, and injectable DTwP-HB-Hib and pneumococcal conjugate vaccine in the contralateral thigh by the intramuscular route. Blood samples were collected at baseline before the first dose and at 28 days after the third dose for measuring the neutralising antibodies against each poliovirus serotype using microneutralisation assay. The site staff evaluating the study outcomes, participants' parents, and the laboratory personnel were masked to the vaccine allocations. The primary outcome of type-specific percentage seroconversion at 28 days after the third dose of ds-IPV or IPV (non-inferiority margin ≥10%) and secondary outcomes of type-specific geometric mean titres and percentage seroprotection (titre ≥8) were assessed in the per-protocol population as the primary population and the full analysis population as the supportive population. Secondary outcomes on safety evaluation included immediate, solicited, unsolicited, and serious adverse events. This study is registered with the Clinical Trials Registry of India (CTRI/2022/05/042363), and is complete. FINDINGS: Between May 23, 2022, and April 13, 2024, of the 658 participants screened, 648 were eligible and randomly assigned to ds-IPV (n=324) or IPV (n=324). Consent was withdrawn for five participants after randomisation; thus, a total of 643 infants received ds-IPV (n=323) or IPV (n=320). The seroconversion rates for type 1 poliovirus in the ds-IPV and IPV groups were 283 (94·7% 95% CI 91·5 to 96·9) of 299 participants and 270 (92·8% 89·2 to 95·5) of 291 participants, respectively, with a difference of 1·9 (95% CI -2·1 to 5·8). The seroconversion rates for type 2 poliovirus in the ds-IPV and IPV groups were 287 (96·3% 93·5 to 98·1) of 298 participants and 284 (97·9% 95·6 to 99·2) of 290 participants, respectively, with a difference of -1·6 (-4·7 to 1·5). The seroconversion rates for type 3 poliovirus in the ds-IPV and IPV groups were 291 (97·3% 94·8 to 98·8) of 299 participants and 288 (99·0% 97·0 to 99·8) of 291 participants, respectively, with a difference of -1·6 (-3·8 to 0·5). Solicited events, including tenderness, redness, swelling, and fever, were very common (≥10%) in both vaccine groups. No causally related serious adverse events were reported. INTERPRETATION: ds-IPV was immunologically non-inferior to IPV and had a similar safety profile. The new adjuvanted IPV could become an alternative option to IPV. The availability of ds-IPV will support a constant supply of IPV for use in poliovirus-naive and exposed target populations. FUNDING: Serum Institute of India.