title: Heterologous prime-boost vaccination with DNA and MVA vaccines, expressing HIV-1 subtype C mosaic Gag virus-like particles, is highly immunogenic in mice.
abstract: In an effort to make affordable vaccines suitable for the regions most affected by HIV-1, we have constructed stable vaccines that express an HIV-1 subtype C mosaic Gag immunogen (BCG-GagM, MVA-GagM and DNA-GagM). Mosaic immunogens have been designed to address the tremendous diversity of this virus. Here we have shown that GagM buds from cells infected and transfected with MVA-GagM and DNA-GagM respectively and forms virus-like particles. Previously we showed that a BCG-GagM prime MVA-GagM boost generated strong cellular immune responses in mice. In this study immune responses to the DNA-GagM and MVA-GagM vaccines were evaluated in homologous and heterologous prime-boost vaccinations. The DNA homologous prime boost vaccination elicited predominantly CD8+ T cells while the homologous MVA vaccination induced predominantly CD4+ T cells. A heterologous DNA-GagM prime MVA-GagM boost induced strong, more balanced Gag CD8+ and CD4+ T cell responses and that were predominantly of an effector memory phenotype. The immunogenicity of the mosaic Gag (GagM) was compared to a naturally occurring subtype C Gag (GagN) using a DNA homologous vaccination regimen. DNA-GagN expresses a natural Gag with a sequence that was closest to the consensus sequence of subtype C viruses sampled in South Africa. DNA-GagM homologous vaccination induced cumulative HIV-1 Gag-specific IFN-γ ELISPOT responses that were 6.5-fold higher than those induced by the DNA-GagN vaccination. Similarly, DNA-GagM vaccination generated 7-fold higher levels of cytokine-positive CD8+ T cells than DNA-GagN, indicating that this subtype C mosaic Gag elicits far more potent immune responses than a consensus-type Gag. Cells transfected and infected with DNA-GagM and MVA-GagM respectively, expressed high levels of GagM and produced budding virus-like particles. Our data indicates that a heterologous prime boost regimen using DNA and MVA vaccines expressing HIV-1 subtype C mosaic Gag is highly immunogenic in mice and warrants further investigation in non-human primates.
authors.affiliation: Institute of Infectious Disease and Molecular Medicine and Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Ros
authors.initials: R
authors.lastname: Chapman
authors.affiliation: Institute of Infectious Disease and Molecular Medicine and Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Tsungai Ivai
authors.initials: TI
authors.lastname: Jongwe
authors.affiliation: Institute of Infectious Disease and Molecular Medicine and Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Nicola
authors.initials: N
authors.lastname: Douglass
authors.affiliation: Institute of Infectious Disease and Molecular Medicine and Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Gerald
authors.initials: G
authors.lastname: Chege
authors.affiliation: Institute of Infectious Disease and Molecular Medicine and Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.|National Health Laboratory Services, Groote Schuur Hospital, Cape Town, South Africa.
authors.forename: Anna-Lise
authors.initials: AL
authors.lastname: Williamson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D015870:Gene Expression; D057809:HEK293 Cells; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D051379:Mice; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D014771:Virion / Q000235:genetics*
chemical_list: C560489:MVA vaccine; D019444:Vaccines, DNA; D014765:Viral Vaccines