Development of a CTL epitope-based vaccine for the treatment of HIV infection.

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

Development of a CTL epitope-based vaccine for the treatment of HIV infection.

Conf Adv AIDS Vaccine Dev. 1997 May 4-7;:60. Unique Identifier : AIDSLINE MED/97927040
Wentworth P; Sette A; Southwood S; del Guercio MF; Wong N; Kubo RT; Volenec J; Walker BD; Kalams S; Cotton D; Chesnut RW; Cytel Corporation, San Diego, CA. Fax: (619) 552-8801.

Abstract: Our goal is to develop more effective immunotherapeutics for the treatment of HIV-1 infection by stimulating CTL immunity focused on multiple, conserved CTL epitopes. In order to accomplish this, we have developed a method to identify CTL epitopes derived from highly conserved regions of the HIV-1 virus. This multi-step strategy includes 1) identification of peptides containing MHC binding motifs, 2) testing peptides with motifs for MHC binding affinity, and 3) evaluation of high affinity MHC binding peptides for capacity to elicit CTL responses in HLA transgenic mice. To date, we have identified 28 HLA-A2 motif-containing, conserved peptides which bind with good affinity to A2.1 (less than or equal 500 nM). These 28 peptides were also tested for the capacity to bind to other A2-supertype alleles (A2.2, A2.3, A2.6, and A68.2). A total of 19 of 28 peptides (68%) bound at least 3 of the 5 A2-supertype alleles. These 19 crossreactive peptides were then selected to test for immunogenicity in HLA-A2.1 transgenic mice. Seven of the 19 peptides tested induced primary CTL responses in transgenic mice. Our efforts are now focused on understanding how to best deliver these peptides with enhanced immunogenicity to achieve the broadest and most potent CTL response. One method which is being evaluated involves the linkage of a T helper peptide and two lipid moieties to the CTL peptide epitope. A vaccine of this formulation (CY-2301), containing the HIV-derived CTL epitope pol 476-484, is currently being tested in HIV-infected patients. An alternative method being evaluated involves the use of DNA minigenes. The parameters by which multiple epitopes can be effectively delivered using DNA are being studied.

Keywords: *AIDS Vaccines/THERAPEUTIC USE *Epitopes/IMMUNOLOGY *HIV Infections/THERAPY *T-Lymphocytes, Cytotoxic/IMMUNOLOGY
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