A replication competent adenovirus 5 host range mutant-simian immunodeficiency virus (SIV) recombinant priming/subunit protein boosting vaccine regimen induces broad, persistent SIV-speeific cellular immunity to dominant and subdominant epitopes in Mamu-A*01 Rhesus macaques
A replication competent adenovirus 5 host range mutant-simian immunodeficiency virus (SIV) recombinant priming/subunit protein boosting vaccine regimen induces broad, persistent SIV-speeific cellular immunity to dominant and subdominant epitopes in Mamu-A*01 Rhesus macaques
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DOI：
10.4049/jimmunol.170.8.4281
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发表时间：
2003-04-15
影响因子：
4.4
通讯作者：
Robert-Guroff, M
中科院分区：
文献类型：
--
作者：
Malkevitch, N;Patterson, LJ;Robert-Guroff, M
CTL在控制HIV和SIV感染中起重要作用。为了定量免疫诱导的细胞免疫应答，通过四聚体染色在用腺病毒（Ad）5宿主范围突变体（Ad 5 hr）-SIVenv/rev重组体免疫的九只猕猴中以及在也接受Ad 5 hr-SlVgag重组体的九只猕猴中的四只中评估对亚显性Env p15 m和p54 m表位和/或显性Gag p11 C表位特异的CD 8（+）T细胞。两次Ad 5 hr-SIV重组引发免疫后，用gp 120蛋白或代表CD 4结合结构域的包膜多肽进行两次加强免疫。两只模拟免疫的猕猴作为对照。还通过ELISPOT测定法使用p11 C、p15 m和p54 m肽刺激物和重叠的合并Gag和Env肽评估IFN-γ分泌细胞。如四聚体染色所示，Ad-重组体引发引起能够识别p11 C、p15 m和p54 m表位的高频率的持久性CD 8（+）T细胞。通过体外刺激后四聚体阳性CD 8（+）T细胞的扩增证实了初次免疫后38周记忆细胞的存在。所诱导的SIV特异性CD 8（+）T细胞是功能性的，并且响应于SIV肽刺激而分泌IFN-γ。虽然外周血CD 8（+）T细胞对次优势Env表位的应答水平和频率不如对优势p11 C表位的应答水平和频率高，但在评价淋巴结CD 8（+）T细胞时观察到应答升高。我们的数据证实的效力和持久性的功能性细胞免疫反应引起的复制能力的广告重组引发。引起的细胞免疫是广泛的，并延伸到亚显性表位。
CTL are important in controlling HIV and SIV infection. To quantify cellular immune responses induced by immunization, CD8(+) T cells specific for the subdominant Env p15m and p54m epitopes and/or the dominant Gag p11C epitope were evaluated by tetramer staining in nine macaques immunized with an adenovirus (Ad) 5 host range mutant (Ad5hr)-SIVenv/rev recombinant and in four of nine which also received an Ad5hr-SlVgag recombinant. Two Ad5hr-SIV recombinant priming immunizations were followed by two boosts with gp120 protein or an envelope polypeptide representing the CD4 binding domain. Two mock-immunized macaques served as controls. IFN-gamma-secreting cells were also assessed by ELISPOT assay using p11C, p15m, and p54m peptide stimuli and overlapping pooled Gag and Env peptides. As shown by tetramer staining, Ad-recombinant priming elicited a high frequency of persistent CD8(+) T cells able to recognize p11C, p15m, and p54m epitopes. The presence of memory cells 38 wk postinitial immunization was confirmed by expansion of tetramer-positive CD8(+) T cells following in vitro stimulation. The SIV-specific CD8(+) T cells elicited were functional and secreted IFN-gamma in response to SIV peptide stimuli. Although the level and frequency of response of peripheral blood CD8(+) T cells to the subdominant Env epitopes were not as great as those to the dominant p11C epitope, elevated responses were observed when lymph node CD8(+) T cells were evaluated. Our data confirm the potency and persistence of functional cellular immune responses elicited by replication competent Ad-recombinant priming. The cellular immunity elicited is broad and extends to subdominant epitopes.