8th International AIDS Conference Amsterdam, Netherlands — July 19-24, 1992

Int Conf AIDS 1992 Jul 19-24; 8:We52 (abstract no. WeD 1043)
Miller MD, Yasutomi Y, Shen L, Koenig S, Fuerst T, Woods R, Emini E, Gould-Fogerite S, Mannino RJ, Letvin NL; Harvard Medical School, Southborough, MA.

OBJECTIVE: We assessed the capacity of two types of novel subunit vaccines to generate CD8+ CTL responses in rhesus monkeys: a synthetic peptide/liposome formulation and a live recombinant Bacille Calmette Guerin (BCG) vector.

METHODS: We have previously shown that simian immunodeficiency virus of macaques (SIVmac)-infected rhesus monkeys possessing the major histocompatibility complex (MHC) class I allele Mamu-A*01 develop a gag-specific CD8+ CTL response limited to a 9 amino acid epitope. One group of Mamu-A*01+ animals were immunized with a peptide/liposome immunogen consisting of 100 ug of a 12 amino acid synthetic peptide encompassing a gag CTL epitope (peptide 11C, residues 182-190) encapsulated in a synthetic phospholipid bilayer which includes the Sendai virus fusion and attachment glycoproteins. A second group of animals were immunized with 10(8) cfu of recombinant BCG expressing the SIVmac251 gag p24 coding sequence (rBCG p24) or BCG expressing a non-SIV antigen. CTL responses were examined using target cells either pulsed with peptide or infected with recombinant vaccinia viruses expressing SIVmac gag proteins.

RESULTS: Rhesus monkeys immunized with the peptide 11C/proteoliposome all developed CD8+, MHC class I-restricted CTL responses which recognized peptide 11C-pulsed as well as SIVmac gag-expressing target cells. The response was detected by 1 week after a single i.m. vaccination and required the inclusion of the Sendai glycoproteins within the liposome. Animals immunized with rBCG-p24, but not control BCG organisms, developed CD8+, MHC class I-restricted CTL responses which recognized both SIVmac gag and the immunodominant gag peptide CTL epitope.

CONCLUSIONS: These studies demonstrate the capacity of both a synthetic peptide/proteoliposome formulation and a recombinant bacterial vector, BCG, to elicit anti-viral CD8+, MHC class I-restricted CTL in rhesus monkeys. The capacity of such CTL to contribute toward a protective immune response against an AIDS virus can now be assessed in the macaque monkey model.

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