[MoOrA1092] Correlation of CTL diversification with clinical and lab parameters of AIDS progression in DNA/ MVA vaccinated macaques

14th International AIDS Conference

Barcelona, Spain — July 7-12, 2002

[TITLE:] Correlation of CTL diversification with clinical and lab parameters of AIDS progression in DNA/ MVA vaccinated macaques

[AUTHOR(S):] K.S. MacDonald, J. Su, Y. Xiong, B. Li¹, M. Luscher², R.R. Amara, H.L. Robinson³

Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. MoOrA1092

BACKGROUND: To study the magnitude, diversification, and MHC restriction of CTL responses over time post vaccination and viral challenge, and their correlation with disease suppression.

METHODS: DNA priming followed by a MVA booster vaccine (SIV-Gag-Pol, HIV-1 Env) was used in a SHIV/rhesus macaque model. PBMC's collected at multiple points post SHIV challenge were used to study CTL responses. Using IFN-γ ELISpots CTL responses were assessed using a Gag library (395 peptides, 9-11 mers overlapping by 1) and confirmed individually. MHC typing was performed by SSP PCR and the MHC restriction analysis was done.

RESULTS: Four groups totaling 24 monkeys were tested and MHC genotypes were determined. Group 1 animals were primed with 2.5mg DNA (high dose) intradermally (i.d.) and 6/6 responded to Gag peptides (median response to 6.5 Gag peptides per animal). All 6 of group 2 animals primed with 2.5mg DNA by intramuscular (i.m.) injection (median 7 peptides) and all of group 3 animals with 250 mg DNA (low dose) i.d. showed response to Gag peptides (median 7.5 peptides). 5 out of 6 of group 4 animals immunized with 250mg DNA i.m. responded (median 5 peptides). Multiple new minimal Gag epitopes were identified. Studies are continuing to compare the responses to epitopes across Gag from different time points, to determine if shifts in the specificity of CTL epitope responsiveness is observed. Viral sequencing is also ongoing to determine if viral escape drives a shift in epitope recognition.

CONCLUSIONS: A broad array of anti-SIV Gag CTL responses can be detected more than 1 year post challenge after DNA/MVA vaccination. These CTL responses are associated with persistent low viral load and a lack of disease in all the vaccinated animals except 1 which failed to develop CTL and progressed to AIDS. Ongoing studies are examining the dynamics of epitope specificity and correlation with potential viral CTL escape mutants.

Presenting author: Kelly MacDonald

1University of Toronto, Toronto, Canada.

2University of Toronto; University Health Network, Toronto, Canada.

3Emory University Vaccine Centre; Yerkes Primate Centre, Atlanta, United States; 4 University of Toronto; Mount Sinai Hospital, Rm 1484, Mt. Sinai Hospital, 600 University Ave., Toronto ON, M5G 1X5, Canada.

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