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
03/2007
Journal Article
Authors:
Peters, B.S.;
Jaoko, W.;
Vardas, E.;
Panayotakopoulos, G.;
Fast, P.;
Schmidt, C.;
Gilmour, J.;
Bogoshi, M.;
Manyonyi, O.;
Dally, L.;
Klavinskis, L.;
Farah, B.;
Tarragona, T.;
Bart, P.A.;
Robinson, A.;
Pieterse, C.;
Stevens, W.;
Thomas, R.;
Barin, B.;
Bwayo, J.[...]
Secondary:
Vaccine
Volume:
25
Pagination:
2120-2127
URL:
http://www.ncbi.nlm.nih.gov/pubmed/17250931
Keywords:
Adolescent; Adult; AIDS Vaccines; Epitopes- T-Lymphocyte; Female; HIV-1; Immunization- Secondary; Injections- Intradermal; Injections- Intramuscular; Injections- Subcutaneous; Interferon-gamma; Leukocytes- Mononuclear; Male; Middle Aged; Vaccination
Abstract:
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.
