Phase 1 safety and immunogenicity testing of DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles
Paul A Goepfert, Marnie L Elizaga, Alicia Sato, Li Qin, Massimo Cardinali, Christine M Hay, John Hural, Stephen C DeRosa, Olivier D DeFawe, Georgia D Tomaras, David C Montefiori, Yongxian Xu, Lilin Lai, Spyros A Kalams, Lindsey R Baden, Sharon E Frey, William A Blattner, Linda S Wyatt, Bernard Moss, Harriet L Robinson, National Institute of Allergy and Infectious Diseases HIV Vaccine Trials Network, Paul A Goepfert, Marnie L Elizaga, Alicia Sato, Li Qin, Massimo Cardinali, Christine M Hay, John Hural, Stephen C DeRosa, Olivier D DeFawe, Georgia D Tomaras, David C Montefiori, Yongxian Xu, Lilin Lai, Spyros A Kalams, Lindsey R Baden, Sharon E Frey, William A Blattner, Linda S Wyatt, Bernard Moss, Harriet L Robinson, National Institute of Allergy and Infectious Diseases HIV Vaccine Trials Network
Abstract
Background: Recombinant DNA and modified vaccinia virus Ankara (rMVA) vaccines represent a promising approach to an HIV/AIDS vaccine. This Phase 1 clinical trial compared the safety and immunogenicity of a rMVA vaccine administered with and without DNA vaccine priming
Methods: GeoVax pGA2/JS7 DNA (D) and MVA/HIV62 (M) vaccines encode noninfectious virus-like particles. Intramuscular needle injections were used to deliver placebo, 2 doses of DNA followed by 2 doses of rMVA (DDMM), one dose of DNA followed by 2 doses of rMVA (DMM), or 3 doses of rMVA (MMM) to HIV-seronegative participants.
Results: Local and systemic symptoms were mild or moderate. Immune response rates for CD4 + and CD8 + T cells were highest in the DDMM group and lowest in the MMM group (77% vs 43% CD4 + and 42% vs 17% CD8 +). In contrast, response rates for Env binding and neutralizing Ab were highest in the MMM group. The DMM group had intermediate response rates. A 1/10th-dose DDMM regimen induced similar T cell but reduced Ab response rates compared with the full-dose DDMM.
Conclusions: MVA62 was well tolerated and elicited different patterns of T cell and Ab responses when administered alone or in combination with the JS7 DNA vaccine.
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Source: PubMed