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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Design and preclinical evaluation of a multigene human immunodeficiency virus type 1 subtype C DNA vaccine for clinical trial
Journal of General Virology, Volume 87, No. 2, Year 2006
Notification
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Description
In this study, the design and preclinical development of a multigene human immunodeficiency virus type 1 (HIV-1) subtype C DNA vaccine are described, developed as part of the South African AIDS Vaccine Initiative (SAAVI). Genetic variation remains a major obstacle in the development of an HIV-1 vaccine and recent strategies have focused on constructing vaccines based on the subtypes dominant in the developing world, where the epidemic is most severe. The vaccine, SAAVI DNA-C, contains an equimolar mixture of two plasmids, pTHr.grttnC and pTHr.gp150CT, which express a polyprotein derived from Gag, reverse transcriptase (RT), Tat and Nef, and a truncated Env, respectively. Genes included in the vaccine were obtained from individuals within 3 months of infection and selection was based on closeness to a South African subtype C consensus sequence. All genes were codon-optimized for increased expression in humans. The genes have been modified for safety, stability and immunogenicity. Tat was inactivated through shuffling of gene fragments, whilst maintaining all potential epitopes; the active site of RT was mutated; 124 aa were removed from the cytoplasmic tail of gp160; and Nef and Gag myristylation sites were inactivated. Following vaccination of BALB/c mice, high levels of cytotoxic T lymphocytes were induced against multiple epitopes and the vaccine stimulated strong CD8+ gamma interferon responses. In addition, high titres of antibodies to gp 120 were induced in guinea pigs. This vaccine is the first component of a prime-boost regimen that is scheduled for clinical trials in humans in the USA and South Africa. © 2006 SGM.
Authors & Co-Authors
Burgers, Wendy A.
South Africa, Cape Town
University of Cape Town
van Harmelen, Joanne H.
South Africa, Cape Town
University of Cape Town
Shephard, Enid G.
South Africa, Cape Town
University of Cape Town
South Africa, Tygerberg
South African Medical Research Council
Adams, Craig
South Africa, Cape Town
University of Cape Town
Mgwebi, Thandiswa
South Africa, Cape Town
University of Cape Town
Bourn, William R.
South Africa, Cape Town
University of Cape Town
Hanke, T.
United Kingdom, Oxford
Mrc Weatherall Institute of Molecular Medicine
Williamson, Anna Lise
South Africa, Cape Town
University of Cape Town
South Africa, Observatory
Groote Schuur Hospital
Williamson, Carolyn
South Africa, Cape Town
University of Cape Town
Statistics
Citations: 62
Authors: 9
Affiliations: 4
Identifiers
Doi:
10.1099/vir.0.81379-0
ISSN:
00221317
Research Areas
Genetics And Genomics
Infectious Diseases
Study Locations
Guinea
South Africa