title: DNA-MVA-protein vaccination of rhesus macaques induces HIV-specific immunity in mucosal-associated lymph nodes and functional antibodies.
abstract: Successful future HIV vaccines are expected to generate an effective cellular and humoral response against the virus in both the peripheral blood and mucosal compartments. We previously reported the development of DNA-C and MVA-C vaccines based on HIV-1 subtype C and demonstrated their immunogenicity when given in a DNA prime-MVA boost combination in a nonhuman primate model. In the current study, rhesus macaques previously vaccinated with a DNA-C and MVA-C vaccine regimen were re-vaccinated 3.5years later with MVA-C followed by a protein vaccine based on HIV-1 subtype C envelope formulated with MF59 adjuvant (gp140Env/MF59), and finally a concurrent boost with both vaccines. A single MVA-C re-vaccination elicited T cell responses in all animals similar to previous peak responses, with 4/7 demonstrating responses >1000 SFU/106PBMC. In contrast to an Env/MF59-only vaccine, concurrent boosting with MVA-C and Env/MF59 induced HIV-specific cellular responses in multiple mucosal associated lymph nodes in 6/7 animals, with high magnitude responses in some animals. Both vaccine regimens induced high titer Env-specific antibodies with ADCC activity, as well as neutralization of Tier 1 viruses and modest Tier 2 neutralization. These data demonstrate the feasibility of inducing HIV-specific immunity in the blood and mucosal sites of viral entry by means of DNA and poxvirus-vectored vaccines, in combination with a HIV envelope-based protein vaccine.
authors.affiliation: Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Gerald K
authors.initials: GK
authors.lastname: Chege
authors.affiliation: Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Burgers
authors.affiliation: Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Müller
authors.affiliation: Division of Immunology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Clive M
authors.initials: CM
authors.lastname: Gray
authors.affiliation: Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; South African Medical Research Council, Cape Town, South Africa.
authors.forename: Enid G
authors.initials: EG
authors.lastname: Shephard
authors.affiliation: Glaxo Smith Kline, Cambridge, MA, USA.
authors.forename: Susan W
authors.initials: SW
authors.lastname: Barnett
authors.affiliation: Duke University Medical Center, Durham, NC, USA.
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.affiliation: Duke University Medical Center, Durham, NC, USA.
authors.forename: David
authors.initials: D
authors.lastname: Montefiori
authors.affiliation: Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Williamson
authors.affiliation: Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa. Electronic address: Anna-Lise.Williamson@uct.ac.za.
authors.forename: Anna-Lise
authors.initials: AL
authors.lastname: Williamson
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000096:biosynthesis; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development / Q000276:immunology; D018928:Immunity, Mucosal / Q000187:drug effects*; D007115:Immunization Schedule; D007117:Immunization, Secondary; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D008253:Macaca mulatta; D009092:Mucous Membrane / Q000187:drug effects / Q000276:immunology / Q000821:virology; D011136:Polysorbates / Q000008:administration & dosage; D013185:Squalene / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D019444:Vaccines, DNA; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000096:biosynthesis; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; C089950:MF59 oil emulsion; C560489:MVA vaccine; D011136:Polysorbates; D019444:Vaccines, DNA; D014765:Viral Vaccines; D054299:env Gene Products, Human Immunodeficiency Virus; D013185:Squalene
keywords: HIV vaccines; Nonhuman primates; Poxvirus/protein