Genetic stabilization of attenuated oral vaccines against poliovirus types 1 and 3

Ming Te Yeh, Matthew Smith, Sarah Carlyle, Jennifer L. Konopka-Anstadt, Cara C. Burns, John Konz, Raul Andino () and Andrew Macadam ()
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Ming Te Yeh: University of California, San Francisco
Matthew Smith: National Institute for Biological Standards and Control
Sarah Carlyle: National Institute for Biological Standards and Control
Jennifer L. Konopka-Anstadt: Division of Viral Diseases, Centers for Disease Control and Prevention
Cara C. Burns: Division of Viral Diseases, Centers for Disease Control and Prevention
John Konz: Center for Vaccine Innovation and Access, PATH
Raul Andino: University of California, San Francisco
Andrew Macadam: National Institute for Biological Standards and Control

Nature, 2023, vol. 619, issue 7968, 135-142

Abstract: Abstract Vaccination with Sabin, a live attenuated oral polio vaccine (OPV), results in robust intestinal and humoral immunity and has been key to controlling poliomyelitis. As with any RNA virus, OPV evolves rapidly to lose attenuating determinants critical to the reacquisition of virulence1–3 resulting in vaccine-derived, virulent poliovirus variants. Circulation of these variants within underimmunized populations leads to further evolution of circulating, vaccine-derived poliovirus with higher transmission capacity, representing a significant risk of polio re-emergence. A new type 2 OPV (nOPV2), with promising clinical data on genetic stability and immunogenicity, recently received authorization from the World Health Organization for use in response to circulating, vaccine-derived poliovirus outbreaks. Here we report the development of two additional live attenuated vaccine candidates against type 1 and 3 polioviruses. The candidates were generated by replacing the capsid coding region of nOPV2 with that from Sabin 1 or 3. These chimeric viruses show growth phenotypes similar to nOPV2 and immunogenicity comparable to their parental Sabin strains, but are more attenuated. Our experiments in mice and deep sequencing analysis confirmed that the candidates remain attenuated and preserve all the documented nOPV2 characteristics concerning genetic stability following accelerated virus evolution. Importantly, these vaccine candidates are highly immunogenic in mice as monovalent and multivalent formulations and may contribute to poliovirus eradication.

Date: 2023
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DOI: 10.1038/s41586-023-06212-3

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