Poliopolis

Abstract

Despite global withdrawal of monovalent oral live-attenuated type-2 polio vaccines (OPV2) in May, 2016, recent circulating vaccine-derived type-2 poliovirus (cVDPV2) outbreaks in Africa highlight the danger of polio re-emerging in high-risk populations with low levels of immunity because of poor vaccine coverage.1Mbaeyi C Alleman MM Ehrhardt D et al.Update on vaccine-derived poliovirus outbreaks - Democratic Republic of the Congo and Horn of Africa, 2017–2018.MMWR Morb Mortal Wkly Rep. 2019; 68: 225-230Crossref PubMed Scopus (19) Google Scholar The only appropriate countermeasure to control and minimise spread of such outbreaks is deployment of stockpiled monovalent OPV2 vaccine, but this approach could seed further cVDPV2 outbreaks. An international effort through a scientific consortium of vaccine developers and global agencies, supported by the Bill & Melinda Gates Foundation, has sought to make more stable attenuated vaccine polioviruses for use in outbreaks with minimal risk of generating new cVDPVs.2Bandyopadhyay AS Garon J Seib K Orenstein WA Polio vaccination: past, present and future.Future Microbiol. 2015; 10: 791-808Crossref PubMed Scopus (149) Google Scholar, 3Bandyopadhyay AS Modlin JF Wenger J Gast C Immunogenicity of new primary immunization schedules with inactivated poliovirus vaccine and bivalent oral polio vaccine for the polio endgame: a review.Clin Infect Dis. 2018; 67: S35-S41Crossref PubMed Scopus (19) Google Scholar In pre-clinical models the resulting two novel OPV2 candidates have been shown to be genetically more stable than the Sabin OPV, and so are less likely to revert to neurovirulent strains shed by vaccinees. Going on to demonstrate the safety and immunogenicity of these candidates in humans in the era following global withdrawal of OPV2 and WHO's containment recommendations4The Global Polio Eradication InitiativePolio endgame strategy 2019–2023: eradication, integration, certification and containment.http://polioeradication.org/wp-content/uploads/2019/03/polio-endgame-strategy-2019-2023.pdfDate: April 30, 2019Date accessed: April 25, 2019Google Scholar has posed unique challenges for the conduct of a phase 1 study that starts clinical development. To overcome this, a unique purpose-built contained environment, Poliopolis, was created in the grounds of Antwerp University Hospital in which to perform phase 1 testing of both novel OPV2 candidates in healthy adult volunteers (figure).5Van Damme P De Coster I Bandyopadhyay AS et al.The safety and immunogenicity of two novel live attenuated monovalent (serotype 2) oral poliovirus vaccines in healthy adults: a double-blind, single-centre phase 1 study.Lancet. 2019; 394: 148-158Summary Full Text Full Text PDF PubMed Scopus (80) Google Scholar Two groups of adults spent 4 weeks of foreseen confinement from the outside world, with all biological waste, clothing, food, and water captured for decontamination, to allow monitoring of shedding of the orally administered vaccines without risking environmental release of these genetically engineered polioviruses. The creation of this self-contained unit was achieved in less than 6 months as a successful outcome of a major collaborative effort involving scientists, staff at the University of Antwerp and the university hospital, building contractors, municipality including local police and fire service, the Belgian Government, and global partners. Safety of the volunteers and the local community were the paramount considerations, with all medical and psychological aspects considered for the former, and all practical physical barriers in place for the latter. As voluntary confinement of 15 candidates was anticipated to last 28 days, psychological assessment at screening was an important factor in the selection process. Without connections to water or sewage infrastructure, the local population was protected from accidental release of the novel viruses. The accomplishment of this innovative clinical trial will lead to further and larger planned assessments of both vaccine candidates in other age cohorts and hopefully eventually ensure their suitability for deployment as the first line of defence against cVDPV2 outbreaks. The successful clinical development process of these vaccines is expected to be instrumental in ensuring long-term success of completing poliovirus eradication. We declare no competing interests.