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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.
- Source :
-
Viruses [Viruses] 2019 Feb 16; Vol. 11 (2). Date of Electronic Publication: 2019 Feb 16. - Publication Year :
- 2019
-
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.
- Subjects :
- Animals
Antibodies, Neutralizing immunology
Female
HIV Infections immunology
HIV Infections prevention & control
HIV-1
Immunity, Cellular
Immunity, Humoral
Immunogenicity, Vaccine
Mice, Inbred BALB C
Vaccines, DNA immunology
Vaccinia virus
env Gene Products, Human Immunodeficiency Virus genetics
gag Gene Products, Human Immunodeficiency Virus genetics
AIDS Vaccines immunology
HIV Antibodies immunology
T-Lymphocytes immunology
Vaccines, Virus-Like Particle immunology
env Gene Products, Human Immunodeficiency Virus immunology
gag Gene Products, Human Immunodeficiency Virus immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1999-4915
- Volume :
- 11
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Viruses
- Publication Type :
- Academic Journal
- Accession number :
- 30781504
- Full Text :
- https://doi.org/10.3390/v11020160