AEGiS-13IAC: A vaccine targeting the gp120 CD4 binding site does not protect against SIV.

13th International AIDS Conference

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

A vaccine targeting the gp120 CD4 binding site does not protect against SIV.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. TuOrA292)

Robert-Guroff M, Patterson LJ, Robey FA, Muck A, Aldrich K, Richardson ES, Markham PD, Cranage M
M. Robert-Guroff, NIH, National Cancer Institute, 41 Library Drive, Building 41, room D804, Bethesda, MD 20892-5055, United States, Tel.: +1 301 496 2114, Fax: +1 301 496 8394, E-mail: guroffm@exchange.nih.gov

BACKGROUND: We assessed immunogenicity and protective efficacy of a peptide polymer (peptomer), representing the SIV gp120 CD4 binding site. The peptomer mimics gp120 alpha-helical structure, binds CD4, and contains B- and T-cell epitopes. It should elicit broadly reactive, conformationally dependent antibody, and strong cellular immunity.

METHODS: Three rhesus macaques were immunized orally and intranasally, then intratracheally, with Ad5hrSIVenv, and boosted 3 times intramuscularly with peptomer in RIBI's adjuvant. The 3rd boost also consisted of peptomer on aluminum oxide nanoparticles given intradermally. Three controls received vector and adjuvant. An SIVmac251(32H) challenge (20 MID50) was given rectally. Animals were assessed immunologically and virologically during immunization and post-challenge.

RESULTS: All immunized macaques exhibited SIV-specific T-cell proliferation (S.I.s:14 to 25) and peptomer binding (but not SIV-neutralizing) antibody; CTL activity ranged from 16 to 53% lysis in 2 of the 3 animals. The immunized macaques were infected post-challenge and showed greater viremia than controls. To explain the higher viral loads we looked for enhancing antibodies which may have triggered a conformational change to allow co-receptor binding and for increased apoptosis stemming from greater T-cell proliferation. No differences compared to controls were seen. Early data with co-receptor-expressing HOS cells suggest primary isolates from the immunized infected animals are CD4 independent.

CONCLUSIONS: Ad5hrSIVenv priming and peptomer boosting elicited binding antibody and strong cellular immunity against epitopes in the CD4 binding region of gp120 but did not prevent SIV infection. Antibodies to this region may have selected for CD4 independent viruses in the immunized, infected animals. The SIV model may be inappropriate for analysis of vaccines targeting the CD4 binding site.

Keywords: AEGIS, SIV, Antigens, CD4, SAIDS Vaccines, Vaccines, Macaca mulatta, Viral Envelope Proteins, Naphthalenes, Vaccines, Synthetic, Viral Vaccines, Vaccination, Vaccines, Attenuated, Macaca, Epitopes, T-Lymphocyte, Immunization, Greece, simian immunodeficiency virus gp120, protect, Animal, immunology
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TuOrA292