Intramuscular versus intradermal administration of fractional dose inactivated poliovirus vaccine in Mozambique, 2020-2022: an, open-label, non-inferiority, randomised, controlled phase 2 trial.

Background: The development of fractional-dose inactivated poliovirus vaccine (fIPV, a fifth of a full IPV dose) has provided a dose-stretching, less costly, and immunogenic alternative to full dose IPV, enhancing global IPV introduction and accessibility. fIPV is administered intradermally, however, intradermal injection is considered difficult and requires skilled administration. This study aimed at assessing the non-inferiority of intramuscular versus intradermal administration of fIPV in young infants in Maputo, Mozambique. Methods: This was an open label, randomized, non-inferiority trial conducted between 2020 and 2022 (Ref. NCT04027036). Healthy IPV-naive infants attending routine immunization services were enrolled in the study and block randomized to receive two sequential doses of fIPV (0.1 mL), either intramuscularly or intradermally, at two and four months of age. Blood samples were collected at four timepoints: baseline, two months after the first dose, one week after the second dose, and one month after the second dose. Samples were analyzed via microneutralization assays against all three poliovirus serotypes. The primary endpoint was defined as cumulative seroconversion rates to type 2 poliovirus after administration of two doses of intramuscular versus intradermal fIPV. The study has been completed, and data analyzed per protocol. Findings: 382 infants (49.5% [189/382] female) were enrolled in the study between 12 August 2020 and 31 May 2022. Cumulative type 2 seroconversion after two fIPV doses reached 92.1% (139/151, 95% CI 86.5-95.8) in the intradermal group and 96.1% (148/154, 95% CI 91.7-98.6) in the intramuscular group (=0.15). The most common adverse events were upper respiratory tract infections, not related to the study vaccine. 12 serious adverse events occurred in the study, none were considered to be related to the study vaccines. Interpretation: This is the second study demonstrating non-inferiority of fIPV administered intramuscularly compared with intradermally; and the first study assessing immunogenicity in young infants. The results informed vaccine policymaking, leading to a recent recommendation from the Strategic Advisory Group of Experts on Immunization from WHO on intramuscular administration of fIPV in outbreak response. Funding: World Health Organization.