AEGiS-13IAC: Selection of a representative HIV-1 subtype C isolate for use in the development of candidate vaccines for Southern Africa.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Selection of a representative HIV-1 subtype C isolate for use in the development of candidate vaccines for Southern Africa.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. TuOrA415)

Williamson C, Swanstrom R, Morris L, Thomas R, Ping L-H, Pascual A, Johnston RE, Abdool Karim S
C. Williamson, SAIMR / UCT, SAIMR Virology, Department of Medical Microbiology, University of Cape Town, Observatory, South Africa, Tel.: +27-21-406 6127, Fax: +27-21-448 4110, E-mail: cwilliam@curie.uct.ac.za

BACKGROUND: HIV-1 subtype C accounts for over 90% of infections in Southern Africa. This study aimed to identify subtype C isolates representative of viruses in Southern Africa, for use in the design of candidate vaccines.

METHODS: Samples were collected from 14 commercial sex workers in Kwazulu/Natal who had seroconverted within the previous 6 months. 800 bp regions of the gag, pol and env genes were directly sequenced from RT-PCR products. Sequences were compared to 17 subtype C sequences from asymptomatic individuals from other regions of South Africa, in addition to approximately fifty published sequences from the Southern African region. Virus was isolated from 10 of the 14 seroconvertors using standard co-culture techniques and assayed for CCR5 and CXCR4 usage on co-receptor transfected cell lines.

RESULTS: Phylogenetic analysis classified all 31 isolates as subtype C based on gag, pol and env genes. The South African isolates formed an independent cluster to the Indian subtype C sequences, included for comparative purposes. All isolates from seroconvertors used CCR5 for virus entry. Two isolates (DU151 and DU422) were selected for inclusion into vaccines based on phylogenetic analysis, amino acid similarity to the consensus sequence, R5 phenotype and adequate replication capacity in tissue culture. These isolates showed greater than 98% amino acid identity to consensus South African sequence in pol and gag, and greater than 89% amino acid identity to the South African consensus env sequence. Env, gag and pol genes from these isolates have been inserted into Venezuelan Equine Encephalitis (VEE) replicons to be used as a candidate HIV-1 vaccines.

CONCLUSION: Representative HIV-1 subtype C viruses have been selected, based on genotypic and phenotypic properties, for inclusion into HIV-1 candidate vaccine. Development of VEE replicon vaccines is currently underway, and it is anticipated that phase I trials will occur within the next year.

Keywords: AEGIS, HIV-1, AIDS Vaccines, Genes, env, Genes, pol, Africa, Southern, Virus Replication, South Africa, Greece, genetics, virology
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