Immunogenicity of propagation-restricted vesicular stomatitis virus encoding Ebola virus glycoprotein in guinea pigs.

Locher, Samira; Schweneker, Marc; Hausmann, Jürgen; Zimmer, Gert (2018). Immunogenicity of propagation-restricted vesicular stomatitis virus encoding Ebola virus glycoprotein in guinea pigs. Journal of general virology, 99(7), pp. 866-879. Society for General Microbiology 10.1099/jgv.0.001085

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Vesicular stomatitis virus (VSV) expressing the Ebola virus (EBOV) glycoprotein (GP) in place of the VSV glycoprotein G (VSV/EBOV-GP) is a promising EBOV vaccine candidate which has already entered clinical phase 3 studies. Although this chimeric virus was tolerated overall by volunteers, it still caused viremia and adverse effects such as fever and arthritis, suggesting that it might not be sufficiently attenuated. In this study, the VSV/EBOV-GP vector was further modified in order to achieve attenuation while maintaining immunogenicity. All recombinant VSV constructs were propagated on VSV G protein expressing helper cells and used to immunize guinea pigs via the intramuscular route. The humoral immune response was analysed by EBOV-GP-specific fluorescence-linked immunosorbent assay, plaque reduction neutralization test and in vitro virus-spreading inhibition test that employed recombinant VSV/EBOV-GP expressing either green fluorescent protein or secreted Nano luciferase. Most modified vector constructs induced lower levels of protective antibodies than the parental VSV/EBOV-GP or a recombinant modified vaccinia virus Ankara vector encoding full-length EBOV-GP. However, the VSV/EBOV-GP(F88A) mutant was at least as immunogenic as the parental vaccine virus although it was highly propagation-restricted. This finding suggests that VSV-vectored vaccines need not be propagation-competent to induce a robust humoral immune response. However, VSV/EBOV-GP(F88A) rapidly reverted to a fully propagation-competent virus indicating that a single-point mutation is not sufficient to maintain the propagation-restricted phenotype.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

UniBE Contributor:

Zimmer, Gert

Subjects:

600 Technology > 630 Agriculture

ISSN:

0022-1317

Publisher:

Society for General Microbiology

Language:

English

Submitter:

Monika Mumenthaler

Date Deposited:

17 Dec 2018 09:31

Last Modified:

17 Dec 2018 09:40

Publisher DOI:

10.1099/jgv.0.001085

PubMed ID:

29869979

Uncontrolled Keywords:

Ebola virus biosafety neutralizing antibody reversion vaccinia virus vector vaccine vesicular stomatitis virus viral glycoprotein

BORIS DOI:

10.7892/boris.122117

URI:

https://boris.unibe.ch/id/eprint/122117

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