title: Design and evaluation of multi-gene, multi-clade HIV-1 MVA vaccines.
abstract: Recombinant modified vaccinia virus Ankara (rMVA) expressing HIV-1 genes are promising vaccine candidates. Toward the goal of conducting clinical trials with one or a cocktail of recombinant viruses, four rMVAs expressing env and gag-pol genes from primary HIV-1 isolates representing predominant subtypes from Kenya, Tanzania, Uganda, and Thailand (A, C, D, and CRF01_AE, respectively) were constructed. Efficient expression, processing, and function of Env and Gag were demonstrated. All inserted genes were shown to be genetically stable after repeated passage in cell culture. Strong HIV-specific cellular and humoral immune responses were elicited in mice immunized with each individual vaccine candidate. The MVA/CMDR vaccine candidate expressing CRF01_AE genes has elicited HIV-specific T-cell responses in two independent Phase I clinical trials. Further testing of the other rMVA is warranted.
authors: Laboratory of Viral Diseases, NIAID, NIH, Bethesda, MD, USA. pearl@niaid.nih.gov
authors: Patricia L
authors: PL
authors: Earl
authors: Catherine
authors: C
authors: Cotter
authors: Bernard
authors: B
authors: Moss
authors: Thomas
authors: T
authors: VanCott
authors: Jeffrey
authors: J
authors: Currier
authors: Leigh Anne
authors: LA
authors: Eller
authors: Francine
authors: F
authors: McCutchan
authors: Deborah L
authors: DL
authors: Birx
authors: Nelson L
authors: NL
authors: Michael
authors: Mary A
authors: MA
authors: Marovich
authors: Merlin
authors: M
authors: Robb
authors: Josephine H
authors: JH
authors: Cox
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000818:Animals; D002478:Cells, Cultured; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016296:Mutagenesis; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus; D054301:gag Gene Products, Human Immunodeficiency Virus