AEGiS-15IAC: Novel epitopes and dynamics of epitope-specific CTL responses in DNA/MVA vaccinated, SHIV infected rhesus macaques.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Novel epitopes and dynamics of epitope-specific CTL responses in DNA/MVA vaccinated, SHIV infected rhesus macaques.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. ThOrA1396)

MacDonald KS, Su J, Luscher MA, Xiong Y, Li B, Amara RR, Robinson HL
University of Toronto, Toronto, Canada

BACKGROUND: SIV infection in the rhesus macaque is an important model for the study of the immunodeficiency virus infections. Prime/boost immunized SHIV-infected animals that effectively controlled viral replication over time were examined to determine the breadth and magnitude of CTL responses, and the relationship of epitope-specific CTL responses to disease progression.

METHODS: Animals were immunized using a DNA priming/Modified Vaccinia Ankara boosting strategy and were subsequently challenged with SHIV89.6P. CTL responses were assessed at multiple time points by IFN-γ ELISpot using 395 SIV Gag 9mer overlapping peptides. MHC typing was performed by PCR-SSP and MHC restriction on CTL epitopes was confirmed using single-allele transfectant target cells. Viral sequencing was performed to detect mutations arising over time.

RESULTS: CTL responses were detected 23/24 animals. Several new CTL epitopes were identified, including five restricted by Mamu-B*01 (Gag39-48 NELDRFGLAE, Gag169-177 EVVPGFQAL, Gag198-206 AAMQIIRDI, Gag257-265 IPVGNIYRR and Gag296-304 SYVDRFYKS). A trend towards increased breadth and magnitude of CTL responses was seen among the animals received higher dose of vaccine. Both shift and expansion of epitope-specific CTL responses were observed, including changes coincident with blips of viremia in some animals. Sequencing revealed that viral mutations were commonly detected in these animals, including mutations within known CTL epitopes.

CONCLUSIONS: Anti-SIV CTL responses can be detected up to 82 weeks post challenge associated with persistent low viral load and lack of clinical disease progression. Viral mutations have been documented within CTL epitopes and their correlation with transient viremia is under examination. Novel Mamu-B*01 epitopes will facilitate the examination of epitope-specific responses in non-A*01 animals.

Keywords: AEGIS, Macaca mulatta, SIV, Epitopes, Epitopes, T-Lymphocyte, Viral Load, DNA, Vaccines, DNA, Viremia, Immunodominant Epitopes, Animal, pathogenicity, immunology

040711
ThOrA1396