Wille-Reece Ulrike, Flynn Barbara J, Loré Karin, Koup Richard A, Miles Aaron P, Saul Allan, Kedl Ross M, Mattapallil Joseph J, Weiss Walter R, Roederer Mario, Seder Robert A
Cellular Immunology Section, Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
J Exp Med. 2006 May 15;203(5):1249-58. doi: 10.1084/jem.20052433. Epub 2006 Apr 24.
There is a remarkable heterogeneity in the functional profile (quality) of T cell responses. Importantly, the magnitude and/or quality of a response required for protection may be different depending on the infection. Here, we assessed the capacity of different Toll like receptor (TLR)-binding compounds to influence T helper cell (Th)1 and CD8+ T cell responses when used as adjuvants in nonhuman primates (NHP) with HIV Gag as a model antigen. NHP were immunized with HIV Gag protein emulsified in Montanide ISA 51, an oil-based adjuvant, with or without a TLR7/8 agonist, a TLR8 agonist, or the TLR9 ligand cytosine phosphate guanosine oligodeoxynucleotides (CpG ODN), and boosted 12 wk later with a replication-defective adenovirus-expressing HIV-Gag (rAD-Gag). Animals vaccinated with HIV Gag protein/Montanide and CpG ODN or the TLR7/8 agonist had higher frequencies of Th1 responses after primary immunization compared to all other vaccine groups. Although the rAD-Gag boost did not elevate the frequency of Th1 memory cytokine responses, there was a striking increase in HIV Gag-specific CD8+ T cell responses after the boost in all animals that had received a primary immunization with any of the TLR adjuvants. Importantly, the presence and type of TLR adjuvant used during primary immunization conferred stability and dramatically influenced the magnitude and quality of the Th1 and CD8+ T cell responses after the rAD-Gag boost. These data provide insights for designing prime-boost immunization regimens to optimize Th1 and CD8+ T cell responses.
T细胞反应的功能特征（质量）存在显著的异质性。重要的是，根据感染情况，保护所需反应的强度和/或质量可能有所不同。在此，我们评估了不同的Toll样受体（TLR）结合化合物作为佐剂在以HIV Gag为模型抗原的非人类灵长类动物（NHP）中影响辅助性T细胞（Th）1和CD8 + T细胞反应的能力。用在Montanide ISA 51（一种油基佐剂）中乳化的HIV Gag蛋白免疫NHP，添加或不添加TLR7/8激动剂、TLR8激动剂或TLR9配体胞嘧啶磷酸鸟苷寡脱氧核苷酸（CpG ODN），并在12周后用表达HIV-Gag的复制缺陷型腺病毒（rAD-Gag）进行加强免疫。与所有其他疫苗组相比，用HIV Gag蛋白/Montanide和CpG ODN或TLR7/8激动剂接种的动物在初次免疫后Th1反应的频率更高。尽管rAD-Gag加强免疫并未提高Th1记忆细胞因子反应的频率，但在所有接受过任何TLR佐剂初次免疫的动物加强免疫后，HIV Gag特异性CD8 + T细胞反应显著增加。重要的是，初次免疫期间使用的TLR佐剂的存在和类型赋予了稳定性，并显著影响了rAD-Gag加强免疫后Th1和CD8 + T细胞反应的强度和质量。这些数据为设计初免-加强免疫方案以优化Th1和CD8 + T细胞反应提供了见解。
