A simple, systematic and unbiased approach to developing an HIV vaccine.

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

A simple, systematic and unbiased approach to developing an HIV vaccine.

Conf Adv AIDS Vaccine Dev. 1997 May 4-7;:63. Unique Identifier : AIDSLINE MED/97927043
Johnston SA; Sykes K; Departments of Medicine and Biochemistry, University of; Texas--Southwestern Medical Center, Dallas, TX. Fax: (214) 648-1450.

Abstract: We present our progress on a simple, systematic and unbiased approach to developing an HIV vaccine. It is based on two recent technological advances: Genetic Immunization as a simple method of delivering and testing vaccines and Expression Library Immunization as a method to resolve the best vaccine candidates from a complex mixture corresponding to a whole genome. The basic idea is to construct two types of libraries which span the entire HIV or SIV genomes in a series of overlapping, defined fragments directed library) or as a large collection of random fragments random library). We hypothesis that this is the most likely way to reveal the "Achilles heel" of HIV for a vaccine. We have tested these libraries in mice and conclude that they produce qualitatively and quantitatively different immune responses than the corresponding whole gene or protein inoculations. There is no evidence of immunological interference between library fragments. Quantitatively different B-cell epitope reactivities and isotype profiles are elicited. We show that fragmenting the Gag gene reveals new CTL epitopes not detected with whole gene inoculations. Based on these results we have created HIV-1, HIV-2 and SIV libraries from both directed and random fragments. These libraries have been constructed in plasmids which bias the humoral or cellular immune response. The HIV-1 and HIV-2 libraries have been inoculated into two groups of baboons. In one group the libraries have been co-inoculated with cytokine (GMCSF and IL-12) genetic adjuvants. Both humoral and cellular responses have been detected in the inoculated baboons.

Keywords: *AIDS Vaccines *Drug Design
971130
M97B1180

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