193   Grouping by HLA Class I Supertype Does Not Enhance HLA Associations with CTL Responses to ALVAC-HIV Canarypox Vaccine Components.

T. J. Bender*, J. Tang, C. Rivers, M. J. Mulligan, and R. A. Kaslow.
Univ. of Alabama at Birmingham.

Background:Similarities in peptide binding specificity have been used to group HLA class I alleles into 9 supertypes (A. Sette et al,. Immunogenetics50:201, 1999) whose functional differences could be more informative than those of individual alleles in explaining patterns of class I-mediated CTL response. We examined whether such grouping better accounted for observed associations of single alleles with CTL response to ALVAC-HIV canarypox vaccines.

Methods:Subjects in AVEG protocols 022, 022A, 026, and 029 received ALVAC-HIV recombinant canarypox vaccines (Pasteur Merieux Connaught, Inc.) for prime vaccination; most received subunit glycoprotein boosts (Chiron Vaccines, Inc.). During 2.5 years of follow-up, PBMCs were collected multiple times for analysis of CD8⁺CTL responses to HIV Gag and Env by the standard lysis method (AVEG Central Immunology Laboratory). 292 vaccinees were typed at HLA-A, B, and C loci using medium/high-resolution PCR-based techniques.

Results:In one or more of 3 post-vaccination intervals spanning the 2.5 years, occasional associations of a supertype with significantly more or less frequent CTL responses were seen. In every case, a significant association with 1 or 2 members of the supertype appeared to account for the supertype effect (A1/A*0101, A*3201; A2/A*0201; A3/A*3101,A*6801; A24/A*2402; B58/B*5701). The magnitudes of the supertype associations were typically less than those for the dominant components (e.g. A1 OR = 2.3 [p = 0.001] vs. A*3201 OR = 4.0 [p = 0.004]; response to Env, 2.5 years). For the B27 supertype, specificities other than B*27 alleles actually abolished the protective effect of B*27 itself (supertype OR = 1.3 [p = 0.453] vs. B*27 OR = 4.5 [p = 0.001]; response to Gag, 2.5 years).

Conclusions:Allele-specific rather than shared supertype properties of HLA class I gene products better explained their significant associations with CTL responses to HIV Gag and Env. An epitope approach to vaccine development may need to take account of the distinctive binding characteristics of individual HLA alleles and not simply the broader similarities among supertypes.