An initial examination of the potential role of T-cell immunity in protection against feline immunodeficiency virus (FIV) infection. Issue 12 (14th March 2016)

• Record Type: Journal Article
• Authors: Aranyos, Alek M.; Roff, Shannon R.; Pu, Ruiyu; Owen, Jennifer L.; Coleman, James K.; Yamamoto, Janet K.
• Is Part Of: Vaccine. Volume 34:Issue 12(2016)
• Page Start: 1480
• Page End: 1488
• Publication Date: 2016-03-14
• Subjects: Feline immunodeficiency virus -- Vaccine -- T cell immunity -- Adoptive transfer; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2016.01.017
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: 23/33 recipients of adoptive T-cell transfer from vaccinated donors were protected. 81% (17/21) protection was against homologous FIV (vaccine strain). 50% (6/12) protection was against neutralizing Ab-resistant, different-subtype FIV. Protection required >60% to 100% MHC-matching between each donor-recipient pair. T cells mediate protection conferred by prototype and commercial FIV vaccines. Abstract: The importance of vaccine-induced T-cell immunity in conferring protection with prototype and commercial FIV vaccines is still unclear. Current studies performed adoptive transfer of T cells from prototype FIV-vaccinated cats to partial-to-complete feline leukocyte antigen (FLA)-matched cats a day before either homologous FIVPet or heterologous-subtype pathogenic FIVFC1 challenge. Adoptive-transfer (A-T) conferred a protection rate of 87% (13 of 15, p < 0.001) against FIVPet using the FLA-matched T cells, whereas all 12 control cats were unprotected. Furthermore, A-T conferred protection rate of 50% (6 of 12, p < 0.023) against FIVFC1 using FLA-matched T cells, whereas all 8 control cats were unprotected. Transfer of FLA-matched T and B cells demonstrated that T cells are needed to confer A-T protection. In addition, complete FLA-matching and addition of T-cell numbers >13 × 10 6 cells were required for A-T protection against FIVFC1 strain, reported to be a highly pathogenic virus resistant to vaccine-induced neutralizing-antibodies. The addition of FLA-matched B cells alone was not protective. The poor quality of the anti-FIV T-cell immunity induced by the vaccine likely contributed to the lack of protection in an FLA-matched recipient against FIVFC1 . The quality of the immune response was determined by the presence of high mRNA levels of cytolysin (perforin) and cytotoxins (granzymes A, B, and H) and T helper-1 cytokines (interferon-γ [IFNγ] and IL2). Increased cytokine, cytolysin and cytotoxin production was detected in the donors which conferred protection in A-T studies. In addition, the CD4 + and CD8 + T-cell proliferation and/or IFNγ responses to FIV p24 and reverse transcriptase increased with each year in cats receiving 1X-3X vaccine boosts over 4 years. These studies demonstrate that anti-FIV T-cell immunity induced by vaccination with a dual-subtype FIV vaccine is essential for prophylactic protection against AIDS lentiviruses such as FIV and potentially HIV-1.