Studies of a prophylactic HIV-1 vaccine candidate based on modified vaccinia virus Ankara (MVA) with and without DNA priming: Effects of dosage and route on safety and immunogenicity
- Department for International Development
- Document Type:
- Journal Article
- Thomas, R., Stevens, W., Dally, L., Farah, B., Fast, P. Gilmour, J., Jaoko, W., Bwayo, J., Omosa-Manyonyi, G., Schmidt, C., Barin, B., Hanke, T., McMichael, A.J., Pantaleo, G., Tarragona, T., Vardas, E., Bart, P.A., Bogoshi, M., Klavinskis, L., McIntyre, J.A., Panayotakopoulos, G., Peters, B.S., Pieterse, C., and Robinson, A.
BACKGROUND: Two parallel studies evaluated safety and immunogenicity of a prophylactic HIV-1 vaccine in 192 HIV-seronegative, low-risk volunteers. Modified vaccinia virus Ankara (MVA) and plasmid DNA (pTHr) expressed HIV-1 clade A gag p24 and p17 fused to a string of 25 overlapping CD8+ T cell epitopes (HIVA). METHODS: These studies compared intramuscular, subcutaneous, and intradermal MVA at dosage levels ranging from 5x10(6)-2.5x10(8) pfu. In Study IAVI-010, DNA vaccine was given as a prime at months 0 and 1, followed by MVA as a boost at months 5 and 8. In Study IAVI-011, MVA alone was given at months 0 and 2. Regular safety monitoring was performed. Immunogenicity was measured by the interferon (IFN)-gamma ELISPOT assay on peripheral blood mononuclear cells (PBMC). RESULTS: No serious adverse events were attributed to either vaccine; most adverse events were mild or moderate, although MVA resulted in some severe local reactions. Five vaccine recipients had at least one positive IFN-gamma ELISPOT response, but none were sustained. CONCLUSION: This HIV-1 vaccine candidate was in general safe and well-tolerated. Local reactions were common, but tolerable. Detectable immune responses were infrequent.
Vaccine (2007) 25 (11) 2120-2127 [doi:10.1016/j.vaccine.2006.11.016]
Document Type: Journal Article
Authors: Thomas, R. Stevens, W. Dally, L. Farah, B. Fast, P. Gilmour, J. Jaoko, W. Bwayo, J. Omosa-Manyonyi, G. Schmidt, C. Barin, B. Hanke, T. McMichael, A.J. Pantaleo, G. Tarragona, T. Vardas, E. Bart, P.A. Bogoshi, M. Klavinskis, L. McIntyre, J.A. Panayotakopoulos, G. Peters, B.S. Pieterse, C. Robinson, A.