Intestinal mucosal immune responses to novel oral poliovirus vaccine type 2 in healthy newborns.

Background: Approximately 1.5 billion doses of novel oral polio vaccine type 2 (nOPV2) have been administered in response to circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks since 2021. Although infants are eligible to receive the vaccine from birth, the induction of intestinal mucosal immunity by nOPV2 in newborns has not been directly evaluated.

Methods: In a randomized, placebo-controlled, phase 2 clinical trial in Bangladesh (2020-2021), 215 healthy newborns received two doses of either nOPV2 (n=110) or placebo (sucrose; n=105), at birth (0-3 days) and 4 weeks later. Intestinal mucosal antibody responses were assessed by measuring poliovirus type 2 (PV2)-specific neutralizing activity and immunoglobulin (Ig)A levels in stool collected biweekly from birth to 8-weeks.

Results: Newborns vaccinated with two doses of nOPV2 had strong intestinal mucosal antibody responses that differed significantly from the placebo group (p<0.0001 for PV2-specific neutralization from 2 weeks onward and p≤0.007 for PV2-specific IgA from 4 weeks onward). Positive PV2-specific neutralization in stool (titers ≥16) was detected in 51.8% (57/110) of nOPV2-vaccinated newborns at 4 weeks and 90.0% (99/110) at 8 weeks (4 weeks after the second dose). Notably, PV2-specific antibody titers following the second dose were very similar for newborns who did and did not have first dose responses (p=0.67 for neutralization and p=0.38 for IgA at 8 weeks).

Conclusions: Vaccination with two doses of nOPV2 in neonates induced strong intestinal mucosal antibody responses. In cVDPV2 outbreak settings, neonatal administration of nOPV2 may be a strategy to enhance population-level intestinal mucosal immunity. Trial registration number NCT04693286.