Fifth International Congress Drug Therapy in HIV Infection 22-26 October, 2000 Glasgow, UK

INDUCTION OF PROTECTIVE IMMUNITY AGAINST HIV/AIDS

M. Girard
CERVI, UMR CNRS-BioMérieux, Lyon, France

Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL7.3
AIDS 2000, Oct 22-26;14(Suppl. 4);S9

The most compelling evidence that vaccination can protect from lentivirus infection (or disease) is that immunization with live attenuated, nef-deleted simian immunodeficiency virus SIVmac (dnef vaccine) can provide protection from pathogenic SIV or hybrid SIV/HIV (SHIV) challenges in rhesus macaques. There is evidence that both neutralizing antibodies and cellmediated immunity may play a role in protection. Thus passive immunization with a high dose of broadly cross-neutralizing anti-HIV monoclonal antibodies can provide protection in chimpanzees and macaques against HIV or SHIV challenges, including by the vaginal route.

CD8⁺ CTL responses are temporally associated with the control of viral replication during acute primary infection, and strong CTL responses are observed in long-term nonprogressors as well as in highly-exposed, uninfected African sex workers. T-cells also release chemokines and supressor factors that inhibit HIV replication in vitro. Viral vectors and naked DNA elicit cellular responses but are inefficient at inducing antibodies in primates. In contrast, subunit envelope glycoproteins and virus like particles induce good antibody responses but little CTL. A combination of the two types of immunogens in a prime-boost regimen is capable of inducing both humoral and cellular immune responses. This strategy has been evaluated in humans volunteers in more than 15 trials in France and the USA, using clade B immunogens and live canarypox virus as a vector. The prime boost regimen induced a large repertoire of antibodies, significant T-cell proliferative responses, and CD8⁺ CTL responses in 20 to 40% of vaccinees at any time point. Similar regimens are studied in Thailand and Uganda, using clade Eand clade A-derived immunogens, respectively. A recombinant vaccinia virus vaccine (MVA) expressing clade A antigens will presently be tested in Kenya in combination with a DNA vaccine. Clade C immunogens, including recombinant alphavirus replicons recombinant BCG and attenuated vaccinia virus strains NYVAC and MVA are also in preparation. Finally, the first phase III efficacy trials with a bivalent gp120 subunit vaccine have been initiated last year in the USA with clade B antigens and in Thailand with a mixture of clade B and clade E antigens. In spite of such progress, the development of a simple vaccine capable of inducing cross-neutralizing antibodies against primary virus isolates and broad polyepitopic CD8⁺ T-cell responses in a majority of vaccinees still remains an elusive challenge.

Presenting author: M. Girard

Download Conferences Abstracts

2000-10-22

Originally published in AIDS Volume 14, Supplement 4 and hosted with permission of the publisher Lippincott Williams & Wilkins, 250 Waterloo Road, London, SE1 8RD, UK. Tel: +44 (0)20 7981 0700 Fax: +44 (0) 7981 0701

Copyright © 2000 - Lippincott Williams & Wilkins. All rights reserved. All abstracts from the Fifth International Congress Drug Therapy in HIV Infection, appearing on the AEGiS web site, are protected by United States copyright law and may not be reproduced, distributed, transmitted, displayed, or otherwise published without the prior written permission of Lippincott Williams & Wilkins. You may not alter or remove any trademark, copyright or other notice. However, provided that you maintain all copyright and other notices contained therein, you may download material (one machine readable copy and one print copy per page) for your personal, non-commercial use only.

http://www.aidsonline.com http://www.ovid.com

This information is designed to support, not replace, the relationship that exists between you and your doctor. ©1980, 2005. AEGiS.