Phase 1 safety and immunogenicity testing of DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles

PA Goepfert, ML Elizaga, A Sato, L Qin… - Journal of Infectious …, 2011 - academic.oup.com
PA Goepfert, ML Elizaga, A Sato, L Qin, M Cardinali, CM Hay, J Hural, SC DeRosa…
Journal of Infectious Diseases, 2011academic.oup.com
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 …
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.
Oxford University Press