FEATURES OF THE HIV ENVELOPE AND DEVELOPMENT OF A SUBUNIT VACCINE

Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.

FEATURES OF THE HIV ENVELOPE AND DEVELOPMENT OF A SUBUNIT VACCINE

AIDS Vaccine Research and Clinical Trials. Putney SD and Bolognesi DP, eds. New York, Marcel Dekker, p. 3-61, 1990.. Unique Identifier : AIDSLINE ICDB/91676941
Putney SD; Javaherian K; Rusche J; Matthews T; Bolognesi DP; Repligen Corporation, Cambridge, MA

Abstract: A major question in the development of an HIV vaccine is whether the body can mount an immune response capable of preventing initial infection and, if so, whether cell-mediated or antibody-mediated immunity is required. The characteristics of the HIV envelope, mapping of determinants that are targets for immune responses, and the ways these determinants could be used to design candidate vaccines are reviewed. Topics include the envelope of HIV (structure and binding to CD4 and variability in amino-acid sequence), mechanisms of immune attack on HIV (humoral and cellular immunity), map of immunologic and functional domains of the envelope (neutralization epitopes, T-cell epitopes, CD4 binding, fusion peptide, mechanism of membrane fusion, and other domains), and HIV vaccine development and efficacy testing (eliciting protective immunity, design and testing of vaccine candidates). Vaccine candidates should be designed to elicit both humoral and cellular immunity and epitopes for neutralizing; and antibody-dependent cellular cytotoxicity antibody, as well as helper and cytotoxic T-cell epitopes, should be included in current vaccine candidates. One advantage of a subunit vaccine is that it can be engineered to contain epitopes representing immune targets while eliminating unimportant or potentially detrimental epitopes. Another advantage is that epitopes could be engineered to elicit a response higher than that elicited by the infecting virus. This may be particularly important for HIV, which may not elicit, or elicit only occasionally, protective immunity. Amino-acid sequence variability is a problem that must be overcome; a vaccine must protect against a diverse array of HIV isolates. One possible solution is to devise a subunit immunogen to elicit a protective immune response targeted toward the conserved envelope segments. Another advantage unique to the subunit approach is that detrimental effects of inactivated virus or native viral proteins can be eliminated in the subunit immunogen. Efficacy testing of vaccine candidates is limited severely by the lack of suitable animal models; HIV infects only chimpanzees and gibbon apes which are in short supply and of limited value. Recently, rabbits have been shown to be susceptible to HIV infection, and it may be possible to generate mice that can be infected with HIV. Once the safety of a vaccine candidate is established, it may be reasonable to use a serologic endpoint to determine potential efficacy. (208 Refs)

Keywords: Amino Acid Sequence/GENETICS/IMMUNOLOGY Animal Antigenic Variation/IMMUNOLOGY CD4-Positive T-Lymphocytes/IMMUNOLOGY Epitopes/*IMMUNOLOGY Human HIV/GENETICS/*IMMUNOLOGY HIV Antibodies/*BIOSYNTHESIS HIV Antigens/*IMMUNOLOGY HIV Envelope Protein gp120/GENETICS/IMMUNOLOGY HIV Envelope Protein gp41/GENETICS/IMMUNOLOGY HIV Infections/*IMMUNOLOGY/PREVENTION & CONTROL Molecular Sequence Data T-Lymphocytes, Cytotoxic/*IMMUNOLOGY Viral Envelope Proteins/*IMMUNOLOGY Viral Vaccines/ADMINISTRATION & DOSAGE/*IMMUNOLOGY MONOGRAPH REVIEW
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M91C4070

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