Abstract

Back to the PAG
Back to the session

Adoptive-transfer studies with semi-inbred cats demonstrate lentivirus-specific CD4+perforin+ CTL and CD8+ CD8+granzyme-B+/interferon-gamma+ CTL important for a broadly-effective AIDS vaccine

Presented by Janet Yamamoto, .

Yamamoto J.¹, Pu R.¹, Coleman J.K.¹, Sato E.¹

¹University of Florida, Gainesville FL, United States

Objective: A commercial dual-subtype FIV vaccine, consisting of inactivated subtype-A and -D viruses, conferred protection against homologous- and heterologous-subtype strains. Heterologous-subtype-B protection was not mediated by vaccine-induced antibodies. Hence, the cellular-immune mechanisms of this vaccine protection were evaluated to provide insights to the immunity needed for a broadly-effective HIV-1 vaccine.
Methods: Three adoptive-transfer (A-T) studies were performed with semi-inbred donor-recipient pairs that were MHC-II-matched by mixed leukocyte reaction (MLR). Magnetic-cell-purified B-cell, T-cell, CD4⁺ T-cell, and CD8⁺ T-cell populations from vaccinated donors were transfused intravenously to MLR-matched recipients one day before challenge with homologous FIV_Pet (Studies 1-2) or heterologous-subtype-B pathogenic FIV_FC1 (Study 3). FIV infection was determined by immunoblot analysis for FIV-specific antibodies and by virus isolation of PBMC and lymphoid tissues using reverse-transcriptase and proviral-PCR analyses. Protective mechanisms were characterized by MHC-I/II sequencing and T-cell functional phenotyping.
Results: In Studies 1-2, 7 of 8 recipients of T cells, 2 of 3 recipients of CD4⁺ T cells, and 2 of 3 recipients of CD8⁺ T cells from vaccinated/MLR-matched cats were protected against FIV_Pet, but eight recipients of PBS, B cells from vaccinated/MLR-matched donors, or T cells from nonvaccinated donors were unprotected. Protected recipients and donors were generally matched at MHC-I sequence, while unprotected recipients and donors were unmatched at MHC-I or MHC-II sequence. In Study 3, 3 of 5 recipients of T cells from vaccinated/MLR-matched donors were protected against FIV_FC1, but five recipients of PBS or MLR-unmatched T cells were unprotected. The vaccine-induced CD4⁺ T-cell and CD8⁺ T-cell populations had FIV-specific interferon-g, granzyme-B, and perforin responses, suggesting the role of CD4⁺perforin⁺ cytotoxic T lymphocytes (CTL) and CD8⁺granzyme-B⁺/interferon-g⁺ CTL, respectively.
Conclusions: Vaccine-induced protective immunity was mediated by MHC-restricted, FIV-specific CD4⁺perforin⁺ CTL and CD8⁺granzyme-B⁺/interferon-g⁺ CTL. These are the first studies to demonstrate cellular-immune correlates of vaccine protection against AIDS lentivirus.

Back to the session - Back to the Programme-at-a-Glance