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

Abstract

BackgroundOur understanding of the acquisition of intestinal mucosal immunity and the control of poliovirus replication and transmission in later life is still emerging.MethodsAs 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.ResultsIn 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.InterpretationIn 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.

Mucosal immunity to poliovirus

“…The possibility that induction of mucosal immunity to poliovirus is less robust after infancy is further supported by recent findings from a study of Swedish adults, who had received IPV in childhood as part of routine immunization programs 54 , 55 (Fig. 1 ).…”

“… Clinical trials were conducted to assess induction of polio type-specific immunity in response to immunization and OPV challenge in infants (FIDEC, Chile, Panama) 11 – 13 , children (Lithuania) 51 , and adults (Sweden, Belgium) 54 , 56 . Induction of polio type-specific intestinal immunity for each trial was evaluated in a related set of studies 16 – 18 , 51 , 55 , 57 . Details of the primary immunization schedules and type-specific OPV challenges for each study are published and briefly summarized here.…”

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

“…In the current study, as in others, there was a strong correlation between intestinal poliovirus-specific IgA and neutralization. A study in young Swedish adults who had received IPV in infancy and were challenged with oral monovalent polio type 1 found that they had an even more limited intestinal immune response [ 23 ]. The immunologic mechanisms underlying this immune blockade are under active investigation.…”

Oral rotavirus vaccine shedding as a marker of mucosal immunity

“…Such models require careful ethical consideration, as well as selection, validation, and testing of a proper challenge agent that can reliably cause infection at a predictable attack rate in susceptible individuals without risk of significant disease. CHIMs are often not ethical to perform in children, but use of approved oral vaccines as challenge agents, as have been used extensively in the poliovirus field 5 – 10 , shows promise but remains underexplored in the evaluation of mucosal immunity to RVA and rotavirus CoPs.…”