A human monoclonal antibody binds within the poliovirus receptor-binding site to neutralize all three serotypes

Andrew J. Charnesky, Julia E. Faust, Hyunwook Lee, Rama Devudu Puligedda, Daniel J. Goetschius, Nadia M. DiNunno, Vaskar Thapa, Carol M. Bator, Sung Hyun (Joseph) Cho, Rahnuma Wahid, Kutub Mahmood, Scott Dessain, Konstantin M. Chumakov, Amy Rosenfeld and Susan L. Hafenstein ()
Additional contact information
Andrew J. Charnesky: The Pennsylvania State University
Julia E. Faust: The Pennsylvania State University
Hyunwook Lee: The Pennsylvania State University
Rama Devudu Puligedda: Lankenau Medical Center
Daniel J. Goetschius: The Pennsylvania State University
Nadia M. DiNunno: The Pennsylvania State University
Vaskar Thapa: The Pennsylvania State University
Carol M. Bator: The Pennsylvania State University
Sung Hyun (Joseph) Cho: The Pennsylvania State University
Rahnuma Wahid: PATH
Kutub Mahmood: PATH
Scott Dessain: Lankenau Medical Center
Konstantin M. Chumakov: Laboratory of Method Development, FDA
Amy Rosenfeld: Laboratory of Method Development, FDA
Susan L. Hafenstein: The Pennsylvania State University

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: Abstract Global eradication of poliovirus remains elusive, and it is critical to develop next generation vaccines and antivirals. In support of this goal, we map the epitope of human monoclonal antibody 9H2 which is able to neutralize the three serotypes of poliovirus. Using cryo-EM we solve the near-atomic structures of 9H2 fragments (Fab) bound to capsids of poliovirus serotypes 1, 2, and 3. The Fab-virus complexes show that Fab interacts with the same binding mode for each serotype and at the same angle of interaction relative to the capsid surface. For each of the Fab-virus complexes, we find that the binding site overlaps with the poliovirus receptor (PVR) binding site and maps across and into a depression in the capsid called the canyon. No conformational changes to the capsid are induced by Fab binding for any complex. Competition binding experiments between 9H2 and PVR reveal that 9H2 impedes receptor binding. Thus, 9H2 outcompetes the receptor to neutralize poliovirus. The ability to neutralize all three serotypes, coupled with the critical importance of the conserved receptor binding site make 9H2 an attractive antiviral candidate for future development.

Date: 2023
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DOI: 10.1038/s41467-023-41052-9

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