Abstract
Heterologous prime boost with DNA and recombinant modified vaccinia virus Ankara (rMVA) vaccines is considered as a promising vaccination approach against human immunodeficiency virus (HIV-1). To further enhance the efficacy of DNA-rMVA vaccination, we investigated humoral and cellular immune responses in mice after three sequential immunizations with DNA, a combination of DNA and virus-like particles (VLP), and rMVA expressing HIV-1 89.6 gp120 envelope proteins (Env). DNA prime and boost with a combination of VLP and DNA vaccines followed by an rMVA boost induced over a 100-fold increase in Env-specific IgG antibody titers compared to three sequential immunizations with DNA and rMVA. Cellular immune responses were induced by VLP-DNA and rMVA vaccinations at high levels in CD8 T cells, CD4 T cells, and peripheral blood mononuclear cells secreting interferon (IFN)-γ, and spleen cells producing interleukin (IL)-2, 4, 5 cytokines. This study suggests that a DNA and VLP combination vaccine with MVA is a promising strategy in enhancing the efficacy of DNA-rMVA vaccination against HIV-1.
Highlights
Over 40 million lives have been claimed due to the human immunodeficiency virus (HIV)pandemic around the world, and the numbers of HIV infection keep increasing
This study revealed that use of a combination of DNA and virus-like particles (VLP) vaccine as the first boost in the context of DNA-recombinant modified vaccinia virus Ankara (rMVA)
HIV VLP vaccines presenting HIV-1 89.6 envelope proteins (Env) proteins were produced in Spodoptera frugiperda Sf9 insect cells as described [25,26]
Summary
Over 40 million lives have been claimed due to the human immunodeficiency virus (HIV). Clinical trials using Vaxgen recombinant gp120 HIV Env protein failed to induce protective immune responses [1]. Soluble HIV Env protein vaccines were not effective in inducing cytotoxic CD8 T cell immunity or protective levels of neutralizing antibodies. DNA and recombinant modified vaccinia virus Ankara (rMVA) vaccines are a candidate HIV vaccine inducing both humoral and cellular immunity [12,13]. Developing a vaccine capable of inducing both protective humoral and cellular immune responses is a central challenge for the development of an effective HIV vaccine. This study revealed that use of a combination of DNA and VLP vaccine as the first boost in the context of DNA-rMVA prime boost immunization could provide significantly enhanced humoral IgG antibody responses together with T cell immune responses
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