Speaker
Description
A major determinant for anti-poliovirus immune response is the viral capsid protein VP1. Multiple unexpected amino acid changes within this protein have been identified in wildtype type 1 poliovirus (WPV1) circulating in Pakistan following the removal of type 2 poliovirus from the oral poliovirus vaccine. These amino acid changes map to known antigenic sites as well as a conserved region found at the C-terminus of the VP1protein. Furthermore, viruses with these changes continue to circulate suggesting that these amino acid alterations are fixed. Determining if the immune response elicited following poliovirus vaccination offers reduced protection after infection with these variants of WPV1 is critical for the effectiveness of established diagnostic tools and assessing vaccine effectiveness.
Sequence analysis of the viral capsid protein VP1 from WPV1 isolated in Pakistan between 2012-2021 revealed successive fixation of amino acid changes in the VP1 protein at positions V77I, K101T, V138I, E168G, and L261M. Additionally, clade-defining amino acid alterations within two antigenic sites (S106A, S221T, A222V) were identified. These observations contrast with those made from genomic analysis of WPV1 isolated between 1940 and 2016 that illustrated transient evolution around a unique consensus of amino acids. Accumulation of these unexpected fixed amino acid changes aid in defining the clades of poliovirus that circulate today and is likely driven by the lack of population immunity against type 2 poliovirus.
Neutralization studies and whole genome sequence analysis are required to determine whether these WPV1 variants can escape vaccine-derived immunity. These studies are planned, funded, but not yet complete. We present model-based estimates of the impact on vaccine efficacy and discuss possible implications for global poliovirus eradication efforts. This work underscores the importance of sustained genomic surveillance and continued laboratory innovation to ensure the continued success of eradication initiatives and address challenges posed by poliovirus evolution.
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