Iwamoto Nami, Takahashi Naofumi, Seki Sayuri, Nomura Takushi, Yamamoto Hiroyuki, Inoue Makoto, Shu Tsugumine, Naruse Taeko K, Kimura Akinori, Matano Tetsuro
AIDS Research Center, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo, Japan.
J Virol. 2014 Jan;88(1):425-33. doi: 10.1128/JVI.02634-13. Epub 2013 Oct 23.
For development of an effective T cell-based AIDS vaccine, it is critical to define the antigens that elicit the most potent responses. Recent studies have suggested that Gag-specific and possibly Vif/Nef-specific CD8(+) T cells can be important in control of the AIDS virus. Here, we tested whether induction of these CD8(+) T cells by prophylactic vaccination can result in control of simian immunodeficiency virus (SIV) replication in Burmese rhesus macaques sharing the major histocompatibility complex class I (MHC-I) haplotype 90-010-Ie associated with dominant Nef-specific CD8(+) T-cell responses. In the first group vaccinated with Gag-expressing vectors (n = 5 animals), three animals that showed efficient Gag-specific CD8(+) T-cell responses in the acute phase postchallenge controlled SIV replication. In the second group vaccinated with Vif- and Nef-expressing vectors (n = 6 animals), three animals that elicited Vif-specific CD8(+) T-cell responses in the acute phase showed SIV control, whereas the remaining three with Nef-specific but not Vif-specific CD8(+) T-cell responses failed to control SIV replication. Analysis of 18 animals, consisting of seven unvaccinated noncontrollers and the 11 vaccinees described above, revealed that the sum of Gag- and Vif-specific CD8(+) T-cell frequencies in the acute phase was inversely correlated with plasma viral loads in the chronic phase. Our results suggest that replication of the AIDS virus can be controlled by vaccine-induced subdominant Gag/Vif epitope-specific CD8(+) T cells, providing a rationale for the induction of Gag- and/or Vif-specific CD8(+) T-cell responses by prophylactic AIDS vaccines.
为开发一种有效的基于T细胞的艾滋病疫苗，确定能引发最有效反应的抗原至关重要。最近的研究表明，Gag特异性以及可能的Vif/Nef特异性CD8(+) T细胞在控制艾滋病病毒方面可能很重要。在此，我们测试了通过预防性疫苗接种诱导这些CD8(+) T细胞是否能控制缅甸恒河猴体内的猴免疫缺陷病毒（SIV）复制，这些猴子共享与显性Nef特异性CD8(+) T细胞反应相关的主要组织相容性复合体I类（MHC-I）单倍型90-010-Ie。在第一组接种表达Gag载体的动物中（n = 5只），三只在攻击后急性期显示出高效Gag特异性CD8(+) T细胞反应的动物控制了SIV复制。在第二组接种表达Vif和Nef载体的动物中（n = 6只），三只在急性期引发Vif特异性CD(+) T细胞反应的动物实现了SIV控制，而其余三只具有Nef特异性但无Vif特异性CD8(+) T细胞反应的动物未能控制SIV复制。对18只动物（包括7只未接种疫苗的非控制者和上述11只接种疫苗的动物）的分析显示，急性期Gag和Vif特异性CD8(+) T细胞频率之和与慢性期血浆病毒载量呈负相关。我们的结果表明，艾滋病病毒的复制可由疫苗诱导的亚显性Gag/Vif表位特异性CD8(+) T细胞控制，这为预防性艾滋病疫苗诱导Gag和/或Vif特异性CD8(+) T细胞反应提供了理论依据。
