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Viruses 2019, 11(2), 160; https://doi.org/10.3390/v11020160

A Novel MVA-Based HIV Vaccine Candidate (MVA-gp145-GPN) Co-Expressing Clade C Membrane-Bound Trimeric gp145 Env and Gag-Induced Virus-Like Particles (VLPs) Triggered Broad and Multifunctional HIV-1-Specific T Cell and Antibody Responses

1
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Campus de Cantoblanco, 28049 Madrid, Spain
2
Biocomputing Unit, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Campus de Cantoblanco, 28049 Madrid, Spain
*
Authors to whom correspondence should be addressed.
Received: 22 January 2019 / Revised: 12 February 2019 / Accepted: 13 February 2019 / Published: 16 February 2019
(This article belongs to the Section Antivirals & Vaccines)
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Abstract

The development of an effective Human Immunodeficiency Virus (HIV) vaccine that is able to stimulate both the humoral and cellular HIV-1-specific immune responses remains a major priority challenge. In this study, we described the generation and preclinical evaluation of single and double modified vaccinia virus Ankara (MVA)-based candidates expressing the HIV-1 clade C membrane-bound gp145(ZM96) trimeric protein and/or the Gag(ZM96)-Pol-Nef(CN54) (GPN) polyprotein that was processed to form Gag-induced virus-like particles (VLPs). In vitro characterization of MVA recombinants revealed the stable integration of HIV-1 genes without affecting its replication capacity. In cells that were infected with Env-expressing viruses, the gp145 protein was inserted into the plasma membrane exposing critical epitopes that were recognized by broadly neutralizing antibodies (bNAbs), whereas Gag-induced VLPs were released from cells that were infected with GPN-expressing viruses. VLP particles as well as purified MVA virions contain Env and Gag visualized by immunoelectron microscopy and western-blot of fractions that were obtained after detergent treatments of purified virus particles. In BALB/c mice, homologous MVA-gp145-GPN prime/boost regimen induced broad and polyfunctional Env- and Gag-specific CD4 T cells and antigen-specific T follicular helper (Tfh) and Germinal Center (GC) B cells, which correlated with robust HIV-1-specific humoral responses. Overall, these results support the consideration of MVA-gp145-GPN vector as a potential vaccine candidate against HIV-1. View Full-Text
Keywords: HIV-1; MVA vaccine; Env-gp145; Gag-Pol-Nef; VLPs; immunogenicity; CD4 T cells; Tfh; GC B cells; humoral responses HIV-1; MVA vaccine; Env-gp145; Gag-Pol-Nef; VLPs; immunogenicity; CD4 T cells; Tfh; GC B cells; humoral responses
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Perdiguero, B.; Sánchez-Corzo, C.; Sorzano, C.O.S.; Saiz, L.; Mediavilla, P.; Esteban, M.; Gómez, C.E. A Novel MVA-Based HIV Vaccine Candidate (MVA-gp145-GPN) Co-Expressing Clade C Membrane-Bound Trimeric gp145 Env and Gag-Induced Virus-Like Particles (VLPs) Triggered Broad and Multifunctional HIV-1-Specific T Cell and Antibody Responses. Viruses 2019, 11, 160.

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