title: HIV-1 Subtype C Mosaic Gag Expressed by BCG and MVA Elicits Persistent Effector T Cell Responses in a Prime-Boost Regimen in Mice.
abstract: Over 90% of HIV/AIDS positive individuals in sub-Saharan Africa are infected with highly heterogeneous HIV-1 subtype C (HIV-1C) viruses. One of the best ways to reduce the burden of this disease is the development of an affordable and effective prophylactic vaccine. Mosaic immunogens are computationally designed to overcome the hurdle of HIV diversity by maximizing the expression of potential T cell epitopes. Mycobacterium bovis BCG ΔpanCD auxotroph and modified vaccinia Ankara (MVA) vaccines expressing HIV-1C mosaic Gag (GagM) were tested in a prime-boost regimen to demonstrate immunogenicity in a mouse study. The BCG-GagM vaccine was stable and persisted 11.5 weeks post vaccination in BALB/c mice. Priming with BCG-GagM and boosting with MVA-GagM elicited higher Gag-specific IFN-γ ELISPOT responses than the BCG-GagM only and MVA-GagM only homologous vaccination regimens. The heterologous vaccination also generated a more balanced and persistent CD4+ and CD8+ T cell Gag-specific IFN-γ ELISPOT response with a predominant effector memory phenotype. A Th1 bias was induced by the vaccines as determined by the predominant secretion of IFN-γ, TNF-α, and IL-2. This study shows that a low dose of MVA (104 pfu) can effectively boost a BCG prime expressing the same mosaic immunogen, generating strong, cellular immune responses against Gag in mice. Our data warrants further evaluation in non-human primates. A low dose vaccine would be an advantage in the resource limited countries of sub-Saharan Africa and India (where the predominating virus is HIV-1 subtype C).
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: 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: 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: Shivan
authors.initials: S
authors.lastname: Chetty
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: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D000818:Animals; D001500:BCG Vaccine / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D001500:BCG Vaccine; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D054301:gag Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma