Mucosal or targeted lymph node immunization of macaques with a particulate SIVp27 protein elicits virus-specific CTL in the genito-rectal mucosa and draining lymph nodes.
Mucosal or targeted lymph node immunization of macaques with a particulate SIVp27 protein elicits virus-specific CTL in the genito-rectal mucosa and draining lymph nodes.
复制标题
用颗粒 SIVp27 蛋白对猕猴进行粘膜或靶向淋巴结免疫，可在生殖器直肠粘膜和引流淋巴结中引发病毒特异性 CTL。
作者：
L. Klavinskis;L. Bergmeier;L. Gao;E. Mitchell;R. Ward;G. Layton;R. Brookes;N. Meyers;T. Lehner
HIV的主要传播途径是通过直肠和宫颈阴道粘膜。为了防止艾滋病毒传播到区域淋巴结(LN)，有效的疫苗可能需要刺激直肠或生殖道中的CTL和引流的LN。我们报告了通过直肠-口腔和阴道-口腔途径进行的粘膜免疫。以SIVp27：TY-VLP颗粒疫苗为靶点的髂骨淋巴结免疫，可在局部淋巴结、脾和外周血单核细胞中诱导SIVgag特异性CTL。该疫苗靶向免疫LN可诱导MHC-I类限制性CD8+CTL反应，其中以髂部LN的CTL频率最高。此外，在从直肠和宫颈阴道粘膜洗脱的单个核细胞中建立的短期T细胞系中，检测到SIVgag特异性CTL活性。从直肠粘膜制备的短期细胞系中CTL的相对频率(21/113或18.6%)与从宫颈阴道粘膜制备的短期细胞系中CTL的相对频率(16/79或20.3%)相似。对位于SIVp27内T细胞表位的CTL相对频率的检测表明，AA41-70多肽在髂部LN细胞中的相对频率高于AA121-150多肽，且经直肠和阴道两种途径免疫后均有显著差异(x~2=6.500，P<0.01)。相反，AA41-70肽与PBMC中CTL的相对频率(15.5%)与AA121-150肽诱导的CTL相对频率(17.6%)相当。这项研究提供了新的证据，表明粘膜免疫或靶向免疫可以在直肠和生殖器粘膜、引流的淋巴系统和中枢淋巴系统产生抗SIV CTL。
The major routes of HIV transmission are through the rectal and cervico-vaginal mucosa. To prevent dissemination of HIV to the regional lymph nodes (LNs), an effective vaccine may need to stimulate CTL in the rectal or genital tract and the draining LNs. We report that mucosal immunization by the recto-oral and vagino-oral route or s.c. immunization targeting the iliac LNs with a particulate SIVp27:Ty-VLP vaccine elicits SIVgag-specific CTL in the regional LNs as well as in the spleen and PBMC. Targeted LN immunization with this vaccine elicited MHC class I-restricted CD8+ CTL responses, and the highest frequency of CTL was found in the iliac LNs. Moreover, SIVgag-specific CTL activity was detected in short term T cell lines established in mononuclear cells eluted from the rectal and cervico-vaginal mucosa. The relative frequency of CTL in short term cell lines prepared from the rectal mucosa (21/113 or 18.6%) was similar to that obtained from the cervico-vaginal mucosa (16/79 or 20.3%). Examination of the relative frequency of CTL to the T cell epitopes residing within SIVp27 showed a higher frequency in iliac LN cells to peptide aa 41-70 than in that to peptide aa 121-150, and this was significant after both recto-oral (chi-squared 6.500, p < 0.02) and vagino-oral (chi-squared = 10.391, p < 0.01) immunization. In contrast, the relative frequency of CTL in PBMC to peptide aa 41-70 (15.5%) was comparable to that elicited by peptide aa 121-150 (17.6%). This study provides novel evidence that mucosal or targeted LN immunization can generate anti-SIV CTL in the rectal and genital mucosa, in the draining LNs, and in the central lymphoid system.