Abstract
SummaryBackgroundIdentification of mechanisms that limit poliovirus replication is crucial for informing decisions aimed at global polio eradication. Studies of mucosal immunity induced by oral poliovirus (OPV) or inactivated poliovirus (IPV) vaccines and mixed schedules thereof will determine the effectiveness of different vaccine strategies to block virus shedding. We used samples from a clinical trial of different vaccination schedules to measure intestinal immunity as judged by neutralisation of virus and virus-specific IgA in stools.MethodsIn the FIDEC trial, Latin American infants were randomly assigned to nine groups to assess the efficacy of two schedules of bivalent OPV (bOPV) and IPV and challenge with monovalent type 2 OPV, and stools samples were collected. We selected three groups of particular interest—the bOPV control group (serotypes 1 and 3 at 6, 10, and 14 weeks), the trivalent attenuated OPV (tOPV) control group (tOPV at 6, 10, and 14 weeks), and the bOPV–IPV group (bOPV at 6, 10, and 14 weeks plus IPV at 14 weeks). Neutralising activity and poliovirus type-specific IgA were measured in stool after a monovalent OPV type 2 challenge at 18 weeks of age. Mucosal immunity was measured by in-vitro neutralisation of a type 2 polio pseudovirus (PV2). Neutralisation titres and total and poliovirus-type-specific IgG and IgA concentrations in stools were assessed in samples collected before challenge and 2 weeks after challenge from all participants.Findings210 infants from Guatemala and Dominican Republic were included in this analysis. Of 38 infants tested for mucosal antibody in the tOPV group, two were shedding virus 1 week after challenge, compared with 59 of 85 infants receiving bOPV (p<0·0001) and 53 of 87 infants receiving bOPV–IPV (p<0·0001). Mucosal type 2 neutralisation and type-specific IgA were noted primarily in response to tOPV. An inverse correlation was noted between virus shedding and both serum type 2 neutralisation at challenge (p<0·0001) and mucosal type 2 neutralisation at challenge (p<0·0001).InterpretationMucosal type-2-specific antibodies can be measured in stool and develop in response to receipt of OPV type 2 either in the primary vaccine series or at challenge. These mucosal antibodies influence the amount of virus that is shed in an established infection.FundingBill & Melinda Gates Foundation.
Highlights
As the spread of poliovirus is progressively constrained both geographically and in circulating lineages, crucial decisions are being made about future vaccination strategies to achieve and sustain the final eradication of poliomyelitis.1,2 These plans include elimination of the type 2 component of the trivalent oral attenuated poliovirus vaccine, as recommended by the Strategic Advisory Group of Experts on Immunization, and replacement with bivalent oral poliovirus vaccine accompanied by the introduction of at least one dose of inactivated polio vaccine (IPV) into the regimen, enhanced environmental surveillance, and the eventual elimination of any use of the live oral poliovirus vaccines (OPVs) in immunisation programmes
Added value of this study We present the first data showing the impact of trivalent attenuated oral poliovirus vaccine, bivalent oral poliovirus vaccine, and a combination of bOPV and inactivated poliovirus vaccine (IPV) on intestinal immunity against type 2 poliovirus when administered according to the Expanded Program on Immunization schedule and document the effect of that immunity on subsequent challenge with the proposed outbreak response tool of the future, monovalent oral poliovirus vaccine type 2
586 samples were analysed from 210 infants given bOPV (n=85), trivalent oral attenuated poliovirus vaccine (tOPV) (n=38), or bOPV–IPV (n=87), which represented approximately 40% of the children in each group
Summary
As the spread of poliovirus is progressively constrained both geographically and in circulating lineages, crucial decisions are being made about future vaccination strategies to achieve and sustain the final eradication of poliomyelitis. These plans include elimination of the type 2 component of the trivalent oral attenuated poliovirus vaccine (tOPV), as recommended by the Strategic Advisory Group of Experts on Immunization, and replacement with bivalent oral poliovirus vaccine (bOPV) accompanied by the introduction of at least one dose of inactivated polio vaccine (IPV) into the regimen, enhanced environmental surveillance, and the eventual elimination of any use of the live oral poliovirus vaccines (OPVs) in immunisation programmes. As the spread of poliovirus is progressively constrained both geographically and in circulating lineages, crucial decisions are being made about future vaccination strategies to achieve and sustain the final eradication of poliomyelitis.. As the spread of poliovirus is progressively constrained both geographically and in circulating lineages, crucial decisions are being made about future vaccination strategies to achieve and sustain the final eradication of poliomyelitis.1,2 These plans include elimination of the type 2 component of the trivalent oral attenuated poliovirus vaccine (tOPV), as recommended by the Strategic Advisory Group of Experts on Immunization, and replacement with bivalent oral poliovirus vaccine (bOPV) accompanied by the introduction of at least one dose of inactivated polio vaccine (IPV) into the regimen, enhanced environmental surveillance, and the eventual elimination of any use of the live oral poliovirus vaccines (OPVs) in immunisation programmes. The notion that IPV will be central to maintenance of eradication is based on the potential development of vaccine-associated paralytic polio in OPV recipients, chronic OPV infection in immunodeficient vaccine
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