A J Paramyxovirus-vectored HIV vaccine induces humoral and cellular responses in mice

Abstract

Human immunodeficiency virus (HIV) infects and depletes CD4+ T-cells, resulting in Acquired Immunodeficiency Syndrome (AIDS) and death. Despite numerous clinical trials, there is no licensed HIV vaccine. The HIV envelope glycoprotein (env) is a major target for vaccine development, especially for the development of antibody-mediated protection. In this study, we used J paramyxovirus (JPV) as a viral vector to express HIV-env. We replaced the JPV small hydrophobic (SH) gene with HIV-env (rJPV-env). Intranasal rJPV-env immunization induced anti-HIV-gp120 IgG antibodies in mice. Furthermore, we examined the immunogenicity of homologous and heterologous prime/boost regimens with rJPV-env, parainfluenza virus 5 (rPIV5)-vectored HIV-env, and HIV-Gag-Env virus-like particles (VLPs). The rJPV-env/rPIV5-env heterologous prime/boost regimen induced the strongest humoral and cellular responses. Introducing a third dose of immunization, mice that received a viral-vectored prime had high levels of HIV-env-specific cellular responses, with group rJPV-env/rPIV5-env/VLP having the highest. Together, this work indicates that a heterologous combination of viral-vectored HIV-env vaccines and a HIV-Gag-Env VLP induces high levels of humoral and cellular responses against HIV in mice.