Vaccination with Combination DNA and Virus-Like Particles Enhances Humoral and Cellular Immune Responses upon Boost with Recombinant Modified Vaccinia Virus Ankara Expressing Human Immunodeficiency Virus Envelope Proteins
Sailaja Gangadhara,
Young-Man Kwon,
Subbiah Jeeva,
Fu-Shi Quan,
Baozhong Wang,
Bernard Moss,
Richard W. Compans,
Rama Rao Amara,
M. Abdul Jabbar,
Sang-Moo Kang
Affiliations
Sailaja Gangadhara
Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, 1510 Clifton Rd., Atlanta, GA 30322, USA
Young-Man Kwon
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA
Subbiah Jeeva
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA
Fu-Shi Quan
Department of Medical Zoology, Kyung Hee University School of Medicine, Seoul 130-705, Korea
Baozhong Wang
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA
Bernard Moss
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Richard W. Compans
Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, 1510 Clifton Rd., Atlanta, GA 30322, USA
Rama Rao Amara
Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, 1510 Clifton Rd., Atlanta, GA 30322, USA
M. Abdul Jabbar
Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, 1510 Clifton Rd., Atlanta, GA 30322, USA
Sang-Moo Kang
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA
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.
