AEGiS-13IAC: A novel HIV-tat multiple peptide conjugate system: potential candidate for AIDS vaccine.

13th International AIDS Conference


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

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A novel HIV-tat multiple peptide conjugate system: potential candidate for AIDS vaccine.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. WeOrA478)

Dhawan S, Boykins RA
S. Dhawan, Center for Biologics Evaluation and Research, Food & Drug Admn., 1401 Rockville Pike HFM-315, Rockville, Maryland 20852-1448, United States, Tel.: +1 301 827 0796, Fax: +1 301 480 7928, E-mail: dhawan@cber.fda.gov

BACKGROUND: Tat protein is produced by HIV-infected cells and plays a critical role in the progression of HIV infection. Therefore, immunologic obstruction of Tat as a prophylaxis treatment could reduce the viremia, thereby delay the onset of progression to AIDS.

METHODS: A single synthetic HIV-Tat multiple peptide conjugate system comprising various functional domains of the HIV-Tat protein was constructed. Immune response against this antigen was assessed and generated antisera were tested for their ability to inhibit HIV pathogenesis.

RESULTS: We report here a novel synthetic multiple peptide conjugate system from the HIV-Tat protein (HIV-Tat-MPC). The HIV-Tat-MPC contained highly conserved cysteine-rich (Tat21-40 ) and basic (Tat53-68 ) domains in various HIV-1 isolates, and Tat9-20 from the HIV-1 group O subtype. Immunization of mice with HIV-Tat-MPC revealed each epitope on the construct to induce an effective immune response. Antibodies against HIV-Tat-MPC efficiently neutralized Tat-induced viral activation by HIV-infected monocytes and reduced viral pathogenesis by greater than 75%. In addition, anti-HIV-Tat-MPC inhibited migration and basement membrane (matrigel) invasion by HIV-infected monocytes in response to Tat protein. These results indicate that anti-HIV-Tat-MPC antibodies inhibit viral pathogenesis possibly by blocking functional determinants, and disrupting autocrine and paracrine pathways of the secreted Tat protein.

CONCLUSION: Our results suggest that HIV-Tat multiple peptide conjugate system could provide a potential AIDS vaccine candidate for inducing effective immunoprophylaxis response to reduce progression of the HIV disease.

Keywords: AEGIS, AIDS Vaccines, HIV Infections, Gene Products, tat, HIV-1, AIDS Dementia Complex, HIV Seropositivity, HIV Antibodies, Acquired Immunodeficiency Syndrome, Peptides, Monocytes, Viremia, Epitopes, Animal, Mice, immunologyKWDaegis,aidsvaccines,hivinfections,geneproducts,tat,hiv-1,aidsdementiacomplex,hivseropositivity,hivantibodies,acquiredimmunodeficiencysyndrome,peptides,monocytes,viremia,epitopes,animal,mice,immunology
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WeOrA478

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