Safety and immunogenicity of inactivated human Rotavirus vaccine in young children and infants: a randomized, placebo-controlled, double-blind, phase I clinical trial

Abstract

Inactivated rotavirus vaccines (IRV) are an effective approach for providing protection against the virus. This double-blind, randomised, placebo-controlled, dose-escalation phase I trial evaluated the safety and immunogenicity of IRV in 288 healthy children aged 2–71 months without prior rotavirus vaccination or HIV infection. We stratified participants by age (7–71 months and 2–6 months) and schedule (2 or 3 doses), before randomising them 3:1 to receive one of three antigen doses (80, 160, or 320 ELISA Unit [EU]), or aluminium adjuvanted placebo. The primary endpoints included adverse reactions/events within 30 min post-dose, adverse reactions/events during days 0–7 and 8–28/30 post-dose, and serious adverse events (SAEs) 6 months after the full course. The secondary endpoints were neutralizing antibody (NTA) geometric mean titres (GMT) and seroconversion rates (≥4-fold rise) at day 28 post-final dose. IRV was well tolerated, with no vaccine-related SAEs in any of the cohorts; we observed clinically manageable transient mild-to-moderate fever in the high dose infant group. Dose-dependent increases in NTA and IgG antibody responses were observed across all cohorts. In the 3-dose infant group, the 320 EU dose yielded a GMT of 551.98 (95% CI 338.39 ~ 900.40) compared to 36.17 for placebo, and a seroconversion rate of 83.33% (vs. 10.00% for placebo); the 3-dose schedule outperformed the 2-dose regimen. Our findings confirm that IRV has a favourable safety and immunogenicity profile. This trial is registered with ClinicalTrials.gov (NCT04626856). This double-blind, randomized, placebo-controlled, dose escalation phase I trial evaluates the safety and immunogenicity of an inactivated rotavirus vaccine (IRV) in healthy young children and infants without prior rotavirus vaccination or HIV infection.