title: Broad, high-magnitude and multifunctional CD4+ and CD8+ T-cell responses elicited by a DNA and modified vaccinia Ankara vaccine containing human immunodeficiency virus type 1 subtype C genes in baboons.
abstract: Candidate human immunodeficiency virus (HIV) vaccine regimens based on DNA boosted with recombinant modified vaccinia Ankara (MVA) have been in development for some time, and there is evidence for improved immunogenicity of newly developed constructs. This study describes immune responses to candidate DNA and MVA vaccines expressing multiple genes (gag, RT, tat, nef and env) from HIV-1 subtype C in chacma baboons (Papio ursinus). The vaccine regimen induced (i) strong T-cell responses, with a median of 4103 spot forming units per 10(6) peripheral blood mononuclear cells by gamma interferon (IFN-gamma) ELISPOT, (ii) broad T-cell responses targeting all five vaccine-expressed genes, with a median of 12 peptides targeted per animal and without any single protein dominating the response, (iii) balanced CD4(+) and CD8(+) responses, which produced both IFN-gamma and interleukin (IL)-2, including IL-2-only responses not detected by the ELISPOT assay, (iv) vaccine memory, which persisted 1 year after immunization and could be boosted further, despite strong anti-vector responses, and (v) mucosal T-cell responses in iliac and mesenteric lymph nodes in two animals tested. The majority of peptide responses mapped contained epitopes previously identified in human HIV infection, and two high-avidity HIV epitope responses were confirmed, indicating the utility of the baboon model for immunogenicity testing. Together, our data show that a combination of DNA and MVA immunization induced robust, durable, multifunctional CD4(+) and CD8(+) responses in baboons targeting multiple HIV epitopes that may home to mucosal sites. These candidate vaccines, which are immunogenic in this pre-clinical model, represent an alternative to adenoviral-based vaccines and have been approved for clinical trials.
authors.affiliation: Institute of Infectious Disease and Molecular Medicine and Division of Medical Virology, Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, South Africa.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Burgers
authors.affiliation: Institute of Infectious Disease and Molecular Medicine and Division of Medical Virology, Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, South Africa.
authors.forename: Gerald K
authors.initials: GK
authors.lastname: Chege
authors.affiliation: Institute of Infectious Disease and Molecular Medicine and Division of Medical Virology, Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, South Africa.
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Müller
authors.affiliation: Institute of Infectious Disease and Molecular Medicine and Division of Medical Virology, Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, South Africa.
authors.forename: Joanne H
authors.initials: JH
authors.lastname: van Harmelen
authors.affiliation: National Institute for Communicable Diseases, Johannesburg, South Africa.
authors.forename: Greg
authors.initials: G
authors.lastname: Khoury
authors.affiliation: MRC/UCT Liver Research Centre, University of Cape Town, Observatory, Cape Town 7925, South Africa.|Institute of Infectious Disease and Molecular Medicine and Division of Medical Virology, Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, South Africa.
authors.forename: Enid G
authors.initials: EG
authors.lastname: Shephard
authors.affiliation: National Institute for Communicable Diseases, Johannesburg, South Africa.
authors.forename: Clive M
authors.initials: CM
authors.lastname: Gray
authors.affiliation: Institute of Infectious Disease and Molecular Medicine and Division of Medical Virology, Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, South Africa.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Williamson
authors.affiliation: National Health Laboratory Services, Groote Schuur Hospital, Cape Town, South Africa.|Institute of Infectious Disease and Molecular Medicine and Division of Medical Virology, Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, South Africa.
authors.forename: Anna-Lise
authors.initials: AL
authors.lastname: Williamson
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004196:Disease Outbreaks; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010215:Papio / Q000276:immunology* / Q000821:virology; D014376:Tuberculosis / Q000453:epidemiology; D019444:Vaccines, DNA / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D015699:HIV Envelope Protein gp120; D007376:Interleukin-2; D019444:Vaccines, DNA; D014765:Viral Vaccines; D007371:Interferon-gamma