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. 2019 Aug 28;4(4):e001613.
doi: 10.1136/bmjgh-2019-001613. eCollection 2019.

Intestinal antibody responses to a live oral poliovirus vaccine challenge among adults previously immunized with inactivated polio vaccine in Sweden

Elizabeth B Brickley  1   2 , Ruth I Connor  3 , Wendy F Wieland-Alter  3 , Marc S Collett  4 , Marianne Hartford  5 , Harrie Van Der Avoort  6 , Austin W Boesch  7 , Joshua A Weiner  7 , Margaret E Ackerman  7 , Mark A McKinlay  8 , Minetaro Arita  9 , Ananda S Bandyopadhyay  10 , John F Modlin  10 , Peter F Wright  3
Affiliations

Intestinal antibody responses to a live oral poliovirus vaccine challenge among adults previously immunized with inactivated polio vaccine in Sweden

Elizabeth B Brickley et al. BMJ Glob Health. .

Abstract

Background: Our understanding of the acquisition of intestinal mucosal immunity and the control of poliovirus replication and transmission in later life is still emerging.

Methods: As part of a 2011 randomised, blinded, placebo-controlled clinical trial of the experimental antiviral agent pocapavir (EudraCT 2011-004804-38), Swedish adults, aged 18-50 years, who had previously received four doses of inactivated polio vaccine (IPV) in childhood were challenged with a single dose of monovalent oral polio vaccine type 1 (mOPV1). Using faecal samples collected before and serially, over the course of 45 days, after mOPV1 challenge from a subset of placebo-arm participants who did not receive pocapavir (N=12), we investigated the kinetics of the intestinal antibody response to challenge virus by measuring poliovirus type 1-specific neutralising activity and IgA concentrations.

Results: In faecal samples collected prior to mOPV1 challenge, we found no evidence of pre-existing intestinal neutralising antibodies to any of the three poliovirus serotypes. Despite persistent high-titered vaccine virus shedding and rising serum neutralisation responses after mOPV1 challenge, intestinal poliovirus type 1-specific neutralisation remained low with a titer of ≤18.4 across all time points and individuals. Poliovirus types 1-specific, 2-specific and 3-specific IgA remained below the limit of detection for all specimens collected postchallenge.

Interpretation: In contrast to recent studies demonstrating brisk intestinal antibody responses to oral polio vaccine challenge in young children previously vaccinated with IPV, this investigation finds that adults previously vaccinated with IPV have only modest intestinal poliovirus type 1-specific neutralisation and no IgA responses that are measurable in stool samples following documented mOPV1 infection.

Keywords: clinical trial; immunisation; poliomyelitis; vaccines.

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Conflict of interest statement

Competing interests: MSC is an employee of the drug-developer ViroDefense, sponsor of pocapavir, and reports grants from the Task Force for Global Health during the conduct of this study. ASB and JFM are employees of the Bill & Melinda Gates Foundation, which provided funding for the study.

Figures

Figure 1
Figure 1
Monovalent oral polio vaccine type 1 viral shedding (log10 CCID50 per gram of stool) in the 4 weeks following challenge among the 12 placebo-arm participants in the study sample.
Figure 2
Figure 2
Subject-specific poliovirus type 1-specific serum IgA (dashed line) and stool neutralising antibody titers (solid line) at the time of mOPV1 challenge and in the 45 days after challenge in adults previously vaccinated with four doses of IPV in childhood (N=12). mOPV1, monovalent oral polio vaccine type 1.
Figure 3
Figure 3
Neutralising antibody titers for A/California/04/2009 H1N1 influenza, respiratory syncytial virus (RSV) and poliovirus (PV) types 1, 2 and 3 in stool samples collected 45 days’ postchallenge with monovalent oral polio vaccine type 1 in adults previously vaccinated with four doses of IPV in early childhood (N=12).
See this image and copyright information in PMC

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