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Viruses 2019, 11(2), 159; https://doi.org/10.3390/v11020159

Induction of Tier 1 HIV Neutralizing Antibodies by Envelope Trimers Incorporated into a Replication Competent Vesicular Stomatitis Virus Vector

1
Division of Virology, Medical University of Innsbruck, 6020 Innsbruck, Austria
2
Christian Doppler Laboratory for Viral Immunotherapy of Cancer, Medical University of Innsbruck, 6020 Innsbruck, Austria
3
Central Laboratory Animal Facility, Medical University of Innsbruck, 6020 Innsbruck, Austria
4
Institut de Biologie Structurale (IBS), CNRS, CEA, Université Grenoble Alpes, 38044 Grenoble, France
5
Division of Hematology and Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
6
Dana-Farber Cancer Institute, Harvard Medical School and Harvard School of Public Health, Boston, MA 02215, USA
7
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
8
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
*
Author to whom correspondence should be addressed.
Received: 10 January 2019 / Revised: 4 February 2019 / Accepted: 12 February 2019 / Published: 15 February 2019
(This article belongs to the Special Issue HIV Vaccines)
Full-Text   |   PDF [2519 KB, uploaded 15 February 2019]   |  

Abstract

A chimeric vesicular stomatitis virus with the glycoprotein of the lymphocytic choriomeningitis virus, VSV-GP, is a potent viral vaccine vector that overcomes several of the limitations of wild-type VSV. Here, we evaluated the potential of VSV-GP as an HIV vaccine vector. We introduced genes for different variants of the HIV-1 envelope protein Env, i.e., secreted or membrane-anchored, intact or mutated furin cleavage site or different C-termini, into the genome of VSV-GP. We found that the addition of the Env antigen did not attenuate VSV-GP replication. All HIV-1 Env variants were expressed in VSV-GP infected cells and some were incorporated very efficiently into VSV-GP particles. Crucial epitopes for binding of broadly neutralizing antibodies against HIV-1 such as MPER (membrane-proximal external region), CD4 binding site, V1V2 and V3 loop were present on the surface of VSV-GP-Env particles. Binding of quaternary antibodies indicated a trimeric structure of VSV-GP incorporated Env. We detected high HIV-1 antibody titers in mice and showed that vectors expressing membrane-anchored Env elicited higher antibody titers than vectors that secreted Envs. In rabbits, Tier 1A HIV-1 neutralizing antibodies were detectable after prime immunization and titers further increased after boosting with a second immunization. Taken together, VSV-GP-Env is a promising vector vaccine against HIV-1 infection since this vector permits incorporation of native monomeric and/or trimeric HIV-1 Env into a viral membrane. View Full-Text
Keywords: HIV vaccine; vesicular stomatitis virus; VSV-GP viral vaccine vector; 1086.C HIV-1 Env; broadly neutralizing antibodies HIV vaccine; vesicular stomatitis virus; VSV-GP viral vaccine vector; 1086.C HIV-1 Env; broadly neutralizing antibodies
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Bresk, C.A.; Hofer, T.; Wilmschen, S.; Krismer, M.; Beierfuß, A.; Effantin, G.; Weissenhorn, W.; Hogan, M.J.; Jordan, A.P.O.; Gelman, R.S.; Montefiori, D.C.; Liao, H.-X.; Schmitz, J.E.; Haynes, B.F.; von Laer, D.; Kimpel, J. Induction of Tier 1 HIV Neutralizing Antibodies by Envelope Trimers Incorporated into a Replication Competent Vesicular Stomatitis Virus Vector. Viruses 2019, 11, 159.

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