A Randomized Phase 4 Study of Immunogenicity and Safety After Monovalent Oral Type 2 Sabin Poliovirus Vaccine Challenge in Children Vaccinated with Inactivated Poliovirus Vaccine in Lithuania

Ananda S Bandyopadhyay, Chris Gast, Elizabeth B Brickley, Ricardo Rüttimann, Ralf Clemens, M Steven Oberste, William C Weldon, Margaret E Ackerman, Ruth I Connor, Wendy F Wieland-Alter, Peter Wright, Vytautas Usonis, Ananda S Bandyopadhyay, Chris Gast, Elizabeth B Brickley, Ricardo Rüttimann, Ralf Clemens, M Steven Oberste, William C Weldon, Margaret E Ackerman, Ruth I Connor, Wendy F Wieland-Alter, Peter Wright, Vytautas Usonis

Abstract

Background: Understanding immunogenicity and safety of monovalent type 2 oral poliovirus vaccine (mOPV2) in inactivated poliovirus vaccine (IPV)-immunized children is of major importance in informing global policy to control circulating vaccine-derived poliovirus outbreaks.

Methods: In this open-label, phase 4 study (NCT02582255) in 100 IPV-vaccinated Lithuanian 1-5-year-olds, we measured humoral and intestinal type 2 polio neutralizing antibodies before and 28 days after 1 or 2 mOPV2 doses given 28 days apart and measured stool viral shedding after each dose. Parents recorded solicited adverse events (AEs) for 7 days after each dose and unsolicited AEs for 6 weeks after vaccination.

Results: After 1 mOPV2 challenge, the type 2 seroprotection rate increased from 98% to 100%. Approximately 28 days after mOPV2 challenge 34 of 68 children (50%; 95% confidence interval, 38%-62%) were shedding virus; 9 of 37 (24%; 12%-41%) were shedding 28 days after a second challenge. Before challenge, type 2 intestinal immunity was undetectable in IPV-primed children, but 28 of 87 (32%) had intestinal neutralizing titers ≥32 after 1 mOPV2 dose. No vaccine-related serious or severe AEs were reported.

Conclusions: High viral excretion after mOPV2 among exclusively IPV-vaccinated children was substantially lower after a subsequent dose, indicating induction of intestinal immunity against type 2 poliovirus.

Keywords: immunogenicity; inactivated poliovirus vaccine; oral poliovirus vaccine; poliovirus; vaccine; viral shedding.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Flow chart of the study.
Figure 2.
Figure 2.
Geometric mean titers (GMTs) (with 95% confidence intervals) of neutralizing antibodies against the 3 poliovirus serotypes in the 2 study groups after 1 (red symbols) or 2 (blue symbols) challenge doses of and safety of monovalent type 2 oral poliovirus vaccine (mOPV2).
Figure 3.
Figure 3.
Proportions shedding virus in stool samples over the period after vaccination with monovalent type 2 oral poliovirus vaccine, shown as rate after each dose (with pointwise 95% confidence intervals as shaded areas). The day of cessation was defined as the last day when virus was detected in stool samples, with all following days being negative.

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Source: PubMed

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