DEVELOPMENT OF REPLICATION-COMPETENT VSV-BASED VACCINES FOR PROTECTION AGAINST HANTAVIRUSES

Author

Joshua Ovila Marceau

Year of Award

2016

Document Type

Dissertation

Degree Type

Doctor of Philosophy (PhD)

Degree Name

Biomedical Sciences

Department or School/College

Department of Biomedical and Pharmaceutical Sciences

Committee Co-chair

Heinz Feldmann, Keith Parker

Commitee Members

Ruben M. Ceballos, Brent Ryckman, Scott Wetzel

Abstract

This study looks at the effects of the position and numbers of foreign immunogens in the vesicular stomatitis virus (VSV) genome on vector attenuation and vaccine efficacy. To generate the recombinant vaccine vectors, a VSV Indiana strain was modified by removing the native VSV glycoprotein and replacing it with one or two foreign glycoproteins; one derived from the filovirus Zaire ebolavirus (ZEBOVgp) and the other from the hantavirus Andes virus (ANDVgpc). Two monovalent (rVSVΔG-ANDVgpc and rVSVΔG-ZEBOVgp) and two bivalent (rVSVΔG-ANDVgpc-ZEBOVgp and rVSVΔG-ZEBOVgp-ANDVgpc recombinant vectors were compared. All vectors were attenuated in cell culture and in immunocompetent hamsters when compared to rVSV wildtype (rVSVwt). rVSVΔG-ZEBOVgp and other unrelated monovalent rVSV vectors did show pathogenicity in an immunocompromised mouse model making this model unsuitable for vaccine efficacy testing. rVSV vaccine vector efficacy testing was explored in the established lethal ANDV hamster model. In addition, two routes of immunization, intraperitoneal and intranasal, were compared. The two bivalent vectors both mediated full protection when administered even 3 days prior to ANDV challenge independent of the route of immunization. The monovalent rVSVΔG-ANDVgpc was similarly protective but intranasal immunization showed reduced efficacy when administered close to challenge. The bivalent rVSVΔGZEBOVgp- ANDVgpc was most potent in post-exposure treatment, followed by the monovalent rVSVΔG-ZEBOVgp. The monovalent rVSVΔG-ANDVgpc was least potent in post-exposure treatment. Intraperitoneal immunization was superior over the intranasal route in post-exposure treatment. Our data indicates the benefit of bivalent rVSV vaccine vectors based on the rVSVΔG-ZEBOVgp backbone with the second immunogen expressed in the downstream position in peri-exposure application.

Recommended Citation

Marceau, Joshua Ovila, "DEVELOPMENT OF REPLICATION-COMPETENT VSV-BASED VACCINES FOR PROTECTION AGAINST HANTAVIRUSES" (2016). Graduate Student Theses, Dissertations, & Professional Papers. 10899.
https://scholarworks.umt.edu/etd/10899