Assessing the immunogenicity of three different inactivated polio vaccine schedules for use after oral polio vaccine cessation, an open label, phase IV, randomized controlled trial.

Background: After global oral poliovirus vaccine (OPV) cessation, the Strategic Advisory Group of Experts on Immunization (SAGE) currently recommends a two-dose schedule of inactivated poliovirus vaccine (IPV) beginning ≥14-weeks of age to achieve at least 90% immune response. We aimed to compare the immunogenicity of three different two-dose IPV schedules started before or at 14-weeks of age.

Methods: We conducted a randomized, controlled, open-label, inequality trial at two sites in Dhaka, Bangladesh. Healthy infants at 6-weeks of age were randomized into one of five arms to receive two-dose IPV schedules at different ages with and without OPV. The three IPV-only arms are presented: Arm C received IPV at 14-weeks and 9-months; Arm D received IPV at 6-weeks and 9-months; and Arm E received IPV at 6 and 14-weeks. The primary outcome was immune response defined as seroconversion from seronegative (<1:8) to seropositive (≥1:8) after vaccination, or a four-fold rise in antibody titers and median reciprocal antibody titers to all three poliovirus types measured at 10-months of age.

Findings: Of the 987 children randomized to Arms C, D, and E, 936 were included in the intention-to-treat analysis. At 10-months, participants in Arm C (IPV at 14-weeks and 9-months) had ≥99% cumulative immune response to all three poliovirus types which was significantly higher than the 77-81% observed in Arm E (IPV at 6 and 14-weeks). Participants in Arm D (IPV at 6-weeks and 9-months) had cumulative immune responses of 98-99% which was significantly higher than that of Arm E (p value < 0.0001) but not different from Arm C.

Interpretation: Results support current SAGE recommendations for IPV following OPV cessation and provide evidence that the schedule of two full IPV doses could begin as early as 6-weeks.