8th Conference on Retroviruses and Opportunistic Infections Chicago, IL - February 4 - 8, 2001

Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:49 (abstract no. 22)

S. W. Barnett¹, I. Srivastava¹, L. Stamatatos², J. Zur Megede¹, G. Otten¹, M. Singh¹, D. O'Hagan¹, J. Ulmer¹, and J. Donnelly^1
1Chiron Corp., Emeryville, CA and ²Aaron Diamond AIDS Res. Ctr., The Rockefeller Univ., New York, NY.

BACKGROUND: The challenge for developing effective vaccines against HIV infection and disease lies in the generation of potent, broad, and durable immune responses. Toward this end, the HIV vaccine research group at Chiron has focused on increasing the potency of both DNA and adjuvanted subunit protein vaccine technologies, as stand alone and mixed modality vaccines.

METHODS: High level, Rev-independent gene cassettes that increase the expression efficiency of the HIV-1 gag, pol, and env structural genes 10-1000 fold have been constructed. Delivery methods that improve the in vivo transfection efficiency and, hence, immunogenicity of HIV DNA vaccines 10-100 fold have been developed. The lead DNA delivery method for future preclinical evaluations utilizes adsorption of DNA onto polylactide co-glycolide (PLG) microparticles.

RESULTS: Studies in rodents and primates indicate that PLG-adsorbed DNA vaccines are potent inducers of cytotoxic T-lymphocyte and CD4+ T-helper cell responses against HIV antigens (see abstract by G. Otten et al.). Furthermore, efforts to induce broadly reactive neutralizing antibody responses against primary HIV-1 isolates have been successful. Employing sequence-modified V2-deleted oligomeric (trimeric; o-gp140) Env from the R5 HIV-1_SF162isolate in a DNA prime-protein boost regimen in rhesus macaques, we were able to induce neutralizing antibodies against diverse primary strains and partial protection against intravenous challenge with the pathogenic SHIV_SF162P.

CONCLUSIONS: These results are encouraging for the future development of prophylactic and therapeutic HIV vaccines.

2001-02-04
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Copyright © 2001 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.