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

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Bresk, CA; Hofer, T; Wilmschen, S; Krismer, M; Beierfuß, A; Effantin, G; Weissenhorn, W; Hogan, MJ; Jordan, APO; Gelman, RS; Montefiori, DC; Liao, H-X; Schmitz, JE; Haynes, BF; von Laer, D; Kimpel, J

Published Date

  • February 15, 2019

Published In

Volume / Issue

  • 11 / 2

PubMed ID

  • 30769947

Pubmed Central ID

  • 30769947

Electronic International Standard Serial Number (EISSN)

  • 1999-4915

Digital Object Identifier (DOI)

  • 10.3390/v11020159

Language

  • eng

Conference Location

  • Switzerland