Design and evaluation of multi-gene, multi-clade HIV-1 MVA vaccines.
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.
Earl
Patricia L
PL
Laboratory of Viral Diseases, NIAID, NIH, Bethesda, MD, USA. pearl@niaid.nih.gov
Cotter
Catherine
C
Moss
Bernard
B
VanCott
Thomas
T
Currier
Jeffrey
J
Eller
Leigh Anne
LA
McCutchan
Francine
F
Birx
Deborah L
DL
Michael
Nelson L
NL
Marovich
Mary A
MA
Robb
Merlin
M
Cox
Josephine H
JH
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
D016915:AIDS Vaccines; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus; D054301:gag Gene Products, Human Immunodeficiency Virus