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.

Publication Type
Journal Article
Year of Publication
2007
Authors
Peters, Barry S; Jaoko, Walter; Vardas, Eftyhia; Panayotakopoulos, George; Fast, Patricia; Schmidt, Claudia; Gilmour, Jill; Bogoshi, Mampedi; Omosa-Manyonyi, Gloria; Dally, Len; Klavinskis, Linda; Farah, Bashir; Tarragona, Tony; Bart, Pierre-Alexandre; Robinson, Andrew; Pieterse, Colleen; Stevens, Wendy; Thomas, Richard; Barin, Burc; McMichael, Andrew J; McIntyre, James A; Pantaleo, Giuseppe; Hanke, Tomáš; Bwayo, Job
Secondary
Vaccine
Volume
25
Pagination
2120-7
Date Published
2007 Mar 01
Keywords
Adolescent; Adult; AIDS Vaccines; Epitopes, T-Lymphocyte; Female; HIV-1; Humans; Immunization, Secondary; Injections, Intradermal; Injections, Intramuscular; Injections, Subcutaneous; Interferon-gamma; Leukocytes, Mononuclear; Male; Middle Aged; Vaccination; Vaccines, DNA
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.