Identifying Polio Antibody Binding Signatures are Associated with Protective Poliovirus Neutralization Titers

Mor Gindi ¹ Lilach M. Friedman ¹ Merav Weil ² Aharona Glatman-Freedman ^3,4 Ravit Bassal ^3,4 Javier Martin ⁵ Lester M. Shulman ^2,4 Tomer Hertz ^1,6

¹Department of Microbiology, Immunology and Genetics, and the National Institute for Biotechnology, Ben-Gurion University of the Negev
²Central Virology Laboratory, Public Health Services, Sheba Medical Center
³Israel Center for Disease Control, Ministry of Health, Sheba Medical Center
⁴Department of Epidemiology and Preventive Medicine, School of Public Health, Faculty of Medical and Health Sciences, Tel Aviv University
⁵Division of Virology, National Institute for Biological Standards and Control
⁶Vaccine and Infectious Disease Division, Fred Hutch Caner Research Center

The global effort to eradicate poliomyelitis (polio) through vaccination against polioviruses (PVs) has dramatically reduced disease incidence. However, challenges persist, including the emergence of Vaccine-Derived Polio Viruses (VDPVs) outbreaks and the necessity to maintain high vaccination coverage post-eradication. Currently, protection following vaccination is assessed using a neutralization assay, which requires the use of live polioviruses, is restricted by the WHO to prevent VDPV outbreaks. To address this challenge, we developed PAM – a novel Polio Antigen Microarray antibody binding assay that allows measuring antibody profiles against a broad range of polio antigens in a single assay that does not utilize live polioviruses. The PAM assay includes inactivated polio viral antigens, virus-like particles (VLPs), and synthetic peptides derived from capsid proteins of 7 strains representing all three polio serotypes. Together these provide a comprehensive poliovirus antibody profile.

Using the PAM assay, we characterized the IgG and IgA poliovirus antibody repertoires in serum samples from 223 polio-vaccinated Israeli adults with known neutralization titers, including 81 individuals with neutralizing titers ≤ 8 against one or more serotypes. Significant associations were found between antibody binding to specific antigens and neutralization titers. For instance, IgG and IgA responses to a type 3 oral polio vaccine (OPV) strain antigen correlated with neutralization against all three serotypes (p<0.05). While antibody responses to viral antigens were linked with protection, IgG and IgA responses to specific clusters of linear peptides showed associations with both protection and susceptibility. Using a logistic regression model, we identified multivariate antibody signatures associated with protection across the three poliovirus serotypes. This study highlights the potential of the PAM assay for predicting protection from polioviruses without using live viruses, aiding the global polio eradication effort.