Roff Shannon R, Sanou Missa P, Rathore Mobeen H, Levy Jay A, Yamamoto Janet K
a Department of Infectious Diseases and Pathology; College of Veterinary Medicine; University of Florida ; Gainesville , FL , USA.
Hum Vaccin Immunother. 2015;11(6):1540-56. doi: 10.1080/21645515.2015.1026500.
Cross-reactive peptides on HIV-1 and FIV p24 protein sequences were studied using peripheral blood mononuclear cells (PBMC) from untreated HIV-1-infected long-term survivors (LTS; >10 y of infection without antiretroviral therapy, ART), short-term HIV-1 infected subjects not on ART, and ART-treated HIV-1 infected subjects. IFNγ-ELISpot and CFSE-proliferation analyses were performed with PBMC using overlapping HIV-1 and FIV p24 peptides. Over half of the HIV-1 infected subjects tested (22/31 or 71%) responded to one or more FIV p24 peptide pools by either IFNγ or T-cell proliferation analysis. PBMC and T cells from infected subjects in all 3 HIV(+) groups predominantly recognized one FIV p24 peptide pool (Fp14) by IFNγ production and one additional FIV p24 peptide pool (Fp9) by T-cell proliferation analysis. Furthermore, evaluation of overlapping SIV p24 peptide sequences identified conserved epitope(s) on the Fp14/Hp15-counterpart of SIV, Sp14, but none on Fp9-counterpart of SIV, Sp9. The responses to these FIV peptide pools were highly reproducible and persisted throughout 2-4 y of monitoring. Intracellular staining analysis for cytotoxins and phenotyping for CD107a determined that peptide epitopes from Fp9 and Fp14 pools induced cytotoxic T lymphocyte-associated molecules including perforin, granzyme B, granzyme A, and/or expression of CD107a. Selected FIV and corresponding SIV epitopes recognized by HIV-1 infected patients indicate that these protein sequences are evolutionarily conserved on both SIV and HIV-1 (e.g., Hp15:Fp14:Sp14). These studies demonstrate that comparative immunogenicity analysis of HIV-1, FIV, and SIV can identify evolutionarily-conserved T cell-associated lentiviral epitopes, which could be used as a vaccine for prophylaxis or immunotherapy.
利用未接受抗逆转录病毒治疗（ART）的长期存活的HIV-1感染者（LTS；感染超过10年且未接受抗逆转录病毒治疗）、未接受ART的短期HIV-1感染受试者以及接受ART治疗的HIV-1感染受试者的外周血单个核细胞（PBMC），研究了HIV-1和FIV p24蛋白序列上的交叉反应性肽段。使用重叠的HIV-1和FIV p24肽段对PBMC进行IFNγ-ELISpot和CFSE增殖分析。超过一半接受检测的HIV-1感染受试者（22/31或71%）通过IFNγ或T细胞增殖分析对一个或多个FIV p24肽库产生反应。所有3个HIV阳性组中感染受试者的PBMC和T细胞主要通过IFNγ产生识别一个FIV p24肽库（Fp14），并通过T细胞增殖分析识别另一个FIV p24肽库（Fp9）。此外，对重叠的SIV p24肽序列进行评估，在SIV的Fp14/Hp15对应物Sp14上鉴定出保守表位，但在SIV的Fp9对应物Sp9上未鉴定出保守表位。对这些FIV肽库的反应具有高度可重复性，并在长达2至4年的监测中持续存在。对细胞毒素的细胞内染色分析和对CD107a的表型分析确定，来自Fp9和Fp14肽库的肽表位可诱导细胞毒性T淋巴细胞相关分子，包括穿孔素、颗粒酶B、颗粒酶A和/或CD107a的表达。HIV-1感染患者识别出的选定FIV和相应SIV表位表明，这些蛋白序列在SIV和HIV-1上在进化上是保守的（例如，Hp15:Fp14:Sp14）。这些研究表明，对HIV-1、FIV和SIV进行比较免疫原性分析可识别进化上保守的T细胞相关慢病毒表位，这些表位可作为预防或免疫治疗的疫苗。
