Design and evaluation of multi-gene,multi-clade HIV-1 MVA vaccines |
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| Authors: | Patricia L. Earl Catherine Cotter Bernard Moss Thomas VanCott Jeffrey Currier Leigh Anne Eller Francine McCutchan Deborah L. Birx Nelson L. Michael Mary A. Marovich Merlin Robb Josephine H. Cox |
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| Affiliation: | 1. Laboratory of Viral Diseases, NIAID, NIH, Bethesda, MD, USA;2. Military HIV Research Program, Walter Reed Army Institute of Research, Rockville, MD, USA |
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| 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. |
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| Keywords: | MVA HIV vaccine Immune response |
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