Lyssavirus Vaccine with a Chimeric Glycoprotein Protects across Phylogroups

Authors

Christine R Fisher, Thomas Jefferson UniversityFollow
David E Lowe, Centers for Disease Control and Prevention (CDC)
Todd G Smith, Centers for Disease Control and Prevention (CDC)
Yong Yang, Centers for Disease Control and Prevention (CDC)
Christina L Hutson, Centers for Disease Control and Prevention (CDC)
Christoph Wirblich, Thomas Jefferson UniversityFollow
Gino Cingolani, Thomas Jefferson UniversityFollow
Matthias J. Schnell, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

7-21-2020

Comments

This article is the author’s final published version in Cell Reports, Volume 32, Issue 3, July 2020, Article number 107920.

The published version is available at https://doi.org/10.1016/j.celrep.2020.107920. Copyright © Fisher et al.

Publication made possible in part by support from the Jefferson Open Access Fund

Abstract

Rabies is nearly 100% lethal in the absence of treatment, killing an estimated 59,000 people annually. Vaccines and biologics are highly efficacious when administered properly. Sixteen rabies-related viruses (lyssaviruses) are similarly lethal, but some are divergent enough to evade protection from current vaccines and biologics, which are based only on the classical rabies virus (RABV). Here we present the development and characterization of LyssaVax, a vaccine featuring a structurally designed, functional chimeric glycoprotein (G) containing immunologically important domains from both RABV G and the highly divergent Mokola virus (MOKV) G. LyssaVax elicits high titers of antibodies specific to both RABV and MOKV Gs in mice. Immune sera also neutralize a range of wild-type lyssaviruses across the major phylogroups. LyssaVax-immunized mice are protected against challenge with recombinant RABV and MOKV. Altogether, LyssaVax demonstrates the utility of structural modeling in vaccine design and constitutes a broadened lyssavirus vaccine candidate.

Recommended Citation

Fisher, Christine R; Lowe, David E; Smith, Todd G; Yang, Yong; Hutson, Christina L; Wirblich, Christoph; Cingolani, Gino; and Schnell, Matthias J., "Lyssavirus Vaccine with a Chimeric Glycoprotein Protects across Phylogroups" (2020). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 169.
https://jdc.jefferson.edu/bmpfp/169

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

PubMed ID

32697993

Language

English