Induction of mucosal immunity by inactivated poliovirus vaccine is dependent on previous mucosal contact with live virus

Research Laboratory for Infectious Diseases, National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
The Journal of Immunology (Impact Factor: 4.92). 05/1999; 162(8):5011-8.
Source: PubMed


The inactivated poliovirus vaccine (IPV) is used for protection against poliomyelitis in The Netherlands. It is not clear, however, whether IPV vaccination can lead to priming of the mucosal immune system and the induction of IgA. It has been demonstrated that IPV vaccination is able to induce strong memory IgA responses in the serum of persons who have been naturally exposed to wild-type poliovirus. This has led to the hypothesis that IPV vaccination is able to induce poliovirus-specific IgA at mucosal sites in persons who have been previously primed with live poliovirus at mucosal sites. To test this hypothesis, the kinetics of the IgA response in serum and saliva after IPV vaccination were examined in persons previously vaccinated with oral poliovirus vaccine (OPV) or IPV. ELISA and enzyme-linked immunospot assays were used for the detection of poliovirus-specific IgA responses. In addition, B cell populations were separated on the basis of the expression of mucosal (alpha4beta7 integrin) and peripheral homing receptors (L-selectin). Parenteral IPV vaccination was able to boost systemic and mucosal IgA responses in previously OPV-vaccinated persons only. None of the previously vaccinated IPV recipients responded with the production of IgA in saliva. In agreement with this finding, a large percentage of the poliovirus-specific IgA-producing lymphocytes detected in previous OPV recipients expressed the alpha4beta7 integrin. It is concluded that IPV vaccination alone is insufficient to induce a mucosal IgA response against poliovirus. In mucosally (OPV-) primed individuals, however, booster vaccination with IPV leads to a strong mucosal IgA response.

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    • "Global eradication of virulent poliovirus appears tantalizingly close as measured by the total incidence of polio cases per year, systemic immunity and does not revert to neurovirulence, but has a complex effect on intestinal immunity. IPV-only regimens are apparently inferior as measured by fecal transmission after challenge , but may depend on whether IPV is administered subsequent to doses of OPV [1] [2] [3] [4] [5]. Since a single coordinated global transition to solely administering inactivated vaccine is infeasible, and mass campaigns need repetition, primary vaccination schedules that blend doses of OPV with IPV will be necessary during the transition period. "
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    ABSTRACT: Background: The Polio Endgame strategy includes phased withdrawal of oral poliovirus vaccines (OPV) coordinated with introduction of inactivated poliovirus vaccine (IPV) to ensure population immunity. The impact of IPV introduction into a primary OPV series of immunizations in a developing country is uncertain. Methods: Between May 2011 and November 2012, we enrolled 700 Bangladeshi infant-mother dyads from Dhaka slums into an open-label randomized controlled trial to test whether substituting an injected IPV dose for the standard Expanded Program on Immunization (EPI) fourth tOPV dose at infant age 39 weeks would reduce fecal shedding and enhance systemic immunity. The primary endpoint was mucosal immunity to poliovirus at age one year, measured by fecal excretion of any Sabin virus at five time points up to 25 days post-52 week tOPV challenge, analyzed by the intention to treat principle. Findings: We randomized 350 families to the tOPV and IPV vaccination arms. Neither study arm resulted in superior intestinal protection at 52 weeks measured by the prevalence of infants shedding any of three poliovirus serotypes, but the IPV dose induced significantly higher seroprevalence and seroconversion rates. This result was identical for poliovirus detection by cell culture or RT-qPCR. The non-significant estimated culture-based shedding risk difference was -3% favoring IPV, and the two vaccination schedules were inferred to be equivalent within a 95% confidence margin of -10% to +4%. Results for shedding analyses stratified by poliovirus type were similar. Conclusions: Neither of the vaccination regimens is superior to the other in enhancing intestinal immunity as measured by poliovirus shedding at 52 weeks of age and the IPV regimen provides similar intestinal immunity to the four tOPV series, although the IPV regimen strongly enhances humoral immunity. The IPV-modified regimen may be considered for vaccination programs without loss of intestinal protection.
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    • "In fact, in this respect it is of particular interest that some studies have shown that IPV (administered via the IM route) may indeed ‘prime’ substantial protective intestinal immunity [7]. Furthermore, in tropical developing countries, a supplemental dose of IPV administered to children previously exposed to OPV boosts humoral and intestinal immunity more effectively than a supplemental dose of OPV [5]–[7], [45], [62], which is supported by a study performed in the Netherlands [63]. Thus, it seems reasonable to assume that an IM vaccination with IPV will induce immunity with some ability to interact with the intestinal site and that a simultaneous priming at both the IM and ID site with the same vaccine will increase the intestinal response. "
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    Full-text · Article · Jun 2014 · PLoS ONE
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    • "If OPV-vaccinated adults and/or older children are found to play a significant role in wild-type poliovirus transmission, strategies to boost their intestinal immunity will be warranted. This could include the use of inactivated vaccine, which has been shown to boost mucosal immunity among individuals previously exposed to live polioviruses and does not suffer poor immunogenicity in lower-income settings [79]. "
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