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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.
Humoral responses, T-Lymphocytes, CD4 T cells, Tfh, HIV Infections, Vaccinia virus, immunogenicity, HIV Antibodies, Microbiology, gag Gene Products, Human Immunodeficiency Virus, CD4 T cells; Env-gp145; GC B cells; Gag-Pol-Nef; HIV-1; MVA vaccine; Tfh; VLPs; humoral responses; immunogenicity, Article, Immunogenicity, Vaccine, Vaccines, DNA, VLPs, Animals, Vaccines, Virus-Like Particle, MVA vaccine, AIDS Vaccines, Immunity, Cellular, Mice, Inbred BALB C, humoral responses, env Gene Products, Human Immunodeficiency Virus, Immunogenicity, Antibodies, Neutralizing, QR1-502, Env-gp145, Immunity, Humoral, HIV-1, GC B cells, Female, Gag-Pol-Nef
Humoral responses, T-Lymphocytes, CD4 T cells, Tfh, HIV Infections, Vaccinia virus, immunogenicity, HIV Antibodies, Microbiology, gag Gene Products, Human Immunodeficiency Virus, CD4 T cells; Env-gp145; GC B cells; Gag-Pol-Nef; HIV-1; MVA vaccine; Tfh; VLPs; humoral responses; immunogenicity, Article, Immunogenicity, Vaccine, Vaccines, DNA, VLPs, Animals, Vaccines, Virus-Like Particle, MVA vaccine, AIDS Vaccines, Immunity, Cellular, Mice, Inbred BALB C, humoral responses, env Gene Products, Human Immunodeficiency Virus, Immunogenicity, Antibodies, Neutralizing, QR1-502, Env-gp145, Immunity, Humoral, HIV-1, GC B cells, Female, Gag-Pol-Nef
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