Preclinical Development of Inactivated Rabies Virus-Based Polyvalent Vaccine Against Rabies and Filoviruses.

Authors

• Mallory Willet
• Drishya Kurup
• Amy Papaneri
• Christoph Wirblich
• Jay W Hooper
• Steve A Kwilas
• Rohan Keshwara
• Andrew Hudacek
• Stefanie Beilfuss
• Grit Rudolph
• Elke Pommerening
• Adriaan Vos
• Andreas Neubert
• Peter Jahrling
• Joseph E Blaney
• Reed F Johnson
• Matthias J Schnell

Publication/Presentation Date

10-1-2015

Abstract

We previously described the generation of a novel Ebola virus (EBOV) vaccine based on inactivated rabies virus (RABV) containing EBOV glycoprotein (GP) incorporated in the RABV virion. Our results demonstrated safety, immunogenicity, and protective efficacy in mice and nonhuman primates (NHPs). Protection against viral challenge depended largely on the quality of the humoral immune response against EBOV GP.Here we present the extension and improvement of this vaccine by increasing the amount of GP incorporation into virions via GP codon-optimization as well as the addition of Sudan virus (SUDV) and Marburg virus (MARV) GP containing virions. Immunogenicity studies in mice indicate similar immune responses for both SUDV GP and MARV GP compared to EBOV GP. Immunizing mice with multiple antigens resulted in immune responses similar to immunization with a single antigen. Moreover, immunization of NHP with the new inactivated RABV EBOV vaccine resulted in high titer neutralizing antibody levels and 100% protection against lethal EBOV challenge when applied with adjuvant.Our results indicate that an inactivated polyvalent vaccine against RABV filoviruses is achievable. Finally, the novel vaccines are produced on approved VERO cells and a clinical grade RABV/EBOV vaccine for human trials has been produced.

Volume

212 Suppl 2

Issue

Suppl 2

First Page

414

Last Page

424

ISSN

1537-6613

Published In/Presented At

Willet, M., Kurup, D., Papaneri, A., Wirblich, C., Hooper, J. W., Kwilas, S. A., Keshwara, R., Hudacek, A., Beilfuss, S., Rudolph, G., Pommerening, E., Vos, A., Neubert, A., Jahrling, P., Blaney, J. E., Johnson, R. F., & Schnell, M. J. (2015). Preclinical Development of Inactivated Rabies Virus-Based Polyvalent Vaccine Against Rabies and Filoviruses. The Journal of infectious diseases, 212 Suppl 2(Suppl 2), S414–S424. https://doi.org/10.1093/infdis/jiv251

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

26063224

Department(s)

Administration and Leadership

Document Type

Article