AEGiS-13IAC: Design and development of a VEE replicon vector HIV-1-subtype C vaccine for South Africa.

13th International AIDS Conference


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

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Design and development of a VEE replicon vector HIV-1-subtype C vaccine for South Africa.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. WeOrA476)

Olmsted R, Karim SA, Williamson C, Morris L, Swanstrom R, Fiscus S, Frelinger J, Johnston R
R. Olmsted, AlphaVax, Inc., 710 W. Main Street, Durham, NC 27701, United States, Tel.: +1 919 688 6902, Fax: +1 919 688 7396, E-mail: olmsted@alphavax.com

BACKGROUND: An international collaborative effort to design and develop an HIV-1-subtype C vaccine for use in South Africa was initiated in October 1998 under the support of the International AIDS Vaccine Initiative.

METHODS: The candidate vaccine will be comprised of a mixture of Venezuelan equine encephalitis virus (VEE) replicon particles individually expressing HIV-1 gag, pol or env genes. The three genes were selected based on homology to the consensus sequence generated from primary isolates obtained from recent seroconvertors in Kwazulu/Natal.

RESULTS: Sequence analyses identified the selected genes as subtype C, reflecting the predominate subtype that exists in potential clinical trial sites. VEE replicon particle (VRP) preparations expressing each of the three genes were prepared for in vitro and in vivo characterization. Western blot analysis of Gag-VRP infected cell lysates demonstrated high-level expression of authentic p55. Importantly, two subcutaneous inoculations of 105 infectious units of Gag-VRP induced both vigorous antigen specific CTL and humoral responses in Balb/c mice. Similarly, Pol-VRP and Env-VRP infected cells expressed protein products of predicted size and immunoreactivity. Immunogenicity studies in mice have been initiated with Pol- and Env-VRP and results will be presented.

CONCLUSION: The individual components of the candidate VEE replicon HIV-1-subtype C vaccine have been engineered and characterized. Our goal is to begin Phase I clinical evaluation in the United States and South Africa within the next year.

Keywords: AEGIS, Encephalomyelitis, Venezuelan Equine, HIV-1, Encephalitis Virus, Venezuelan Equine, Replicon, AIDS Vaccines, Vaccination, Clinical Trials, United States, South Africa, In Vitro, Animal, Mice, geneticsKWDaegis,encephalomyelitis,venezuelanequine,hiv-1,encephalitisvirus,venezuelanequine,replicon,aidsvaccines,vaccination,clinicaltrials,unitedstates,southafrica,invitro,animal,mice,genetics
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WeOrA476

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