Supporting the development of new tests to assess mucosal immunity against polio
To date, smallpox is the only human infectious disease which has been eradicated, demonstrating the difficulty of eliminating a microbe from the environment.
All photographs in this article are used with permission from the World Health Organization.
Polio has existed for thousands of years – the first documented case of paralysis, likely from poliovirus, was engraved on an Egyptian tablet dating back to 1580 BC. 
While the Salk inactivated injectable polio vaccine (IPV) and the Sabin live oral polio vaccine (OPV) became available in 1955 and 1961 respectively, a sharp decrease in the prevalence of polio wasn’t realized until the 1970s, when widespread immunization practices were established. Currently, wild polio is only circulating in parts of Afghanistan, Pakistan, and Nigeria, bringing global eradication within sight.
Harish Verma, along with colleagues at the World Health Organization (WHO) Polio Research unit, and collaborators across the globe are hard at work developing and deploying the most effective tools to stop the virus’s transmission.
Building a Better Assay
Mucosal immunity in the gut is critical for individual protection against polio and also to interrupt person-to-person spread of the virus. The gold standard to determine mucosal immunity is a challenge excretion study, where the gut is challenged with live, attenuated vaccine virus and levels of viral replication and shed virus are measured. The WHO Polio Research unit is always in search of new technologies to detect and assess mucosal immunity that are faster, more reproducible, and require less skilled labor than conventional methods.
Margaret Ackerman and Peter Wright from Dartmouth College, in collaboration with Sonia Resik, from the Laboratorio Nacional de Referencia de Poliovirus y otros Enterovirus in Cuba, submitted a proposal to the WHO to develop xMAP®-based polio-specific IgA and novel mucosal neutralization assays. In addition to the potential utility of the multiplex and neutralization assays to assess mucosal immunity, the WHO is also interested in supporting the project to build capacity in Resik’s lab beyond traditional serum-based assays, as she is a frequent collaborator on WHO polio projects as part of The Global Polio Laboratory Network.
Why Cuba?
Cuba provides a unique opportunity to study the development of mucosal polio immunity. In 1963, Cuba interrupted polio virus transmission. To prevent reemergence of the virus, Cubans are vaccinated twice yearly during distinct campaigns with OPV. Outside of the vaccination campaigns, there is no circulation of the vaccine virus in the population and the subsequent birth cohort is by definition immunologically naive. Without a continuous influx of vaccine virus into the population, in collaboration with the Dartmouth group, Resik will be able to determine the role of IPV in mucosal immunity sensitization.
Towards the Next Generation of Polio Vaccine
OPV has long been the formulation of choice in areas with circulating polio as it provides mucosal immunity, hence enabling it to interrupt person-to-person spread of the virus, is less costly, and is easier to administer versus the inactive injectable version. Once polio has been eradicated, OPV will be phased out due to the small risk of vaccine-associated polio infection and paralysis. Once sufficient community immunity is reached, IPV will be used to maintain population immunity to prevent the occurrence of outbreaks.
Unfortunately, there is a shortage of IPVs in the global market. Researchers recently demonstrated that two fractional doses of IPV provide a greater protective effect than a single full dose. Needle adaptors have also been developed to control depth of intradermal injection and needle-free injectors have been developed to support the routine administration of the vaccines, as there are a limited number of trained vaccinators. Efforts around improving vaccine production are also being made, such as the development of safer production practices for Sabin IPV, as well as the manufacture of an IPV with non-infectious viral particles.
The Dartmouth xMAP-based IgA assay and mucosal neutralization development project is nearly underway, with a MAGPIX® instrument awaiting import to Cuba. Verma hopes that understanding how IPV primes the mucosal immune response will aid in the development of the next generation of polio vaccines to protect children in a postpolio world in the most effective manner possible.
