rBCG induces strong antigen-specific T cell responses in rhesus macaques in a prime-boost setting with an adenovirus 35 tuberculosis vaccine vector.
rBCG induces strong antigen-specific T cell responses in rhesus macaques in a prime-boost setting with an adenovirus 35 tuberculosis vaccine vector.
复制标题
DOI：
10.1371/journal.pone.0003790
复制
发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Maeurer, Markus
中科院分区：
文献类型：
--
作者：
Magalhaes, Isabelle;Sizemore, Donata R.;Ahmed, Raija K.;Mueller, Stefanie;Wehlin, Lena;Scanga, Charles;Weichold, Frank;Schirru, Giulia;Pau, Maria Grazia;Goudsmit, Jaap;Kuhlmann-Berenzon, Sharon;Spangberg, Mats;Andersson, Jan;Gaines, Hans;Thorstensson, Rigmor;Skeiky, Yasir A. W.;Sadoff, Jerry;Maeurer, Markus
BCG疫苗接种结合腺病毒递送的加强，代表了增强、扩大和延长针对结核病（TB）的免疫保护的合理策略。我们测试了BCG（SSI 1331）（在6只动物中，皮内递送）和表达产气链球菌溶血素的重组（rBCG）AFRO-1（6只动物），随后两次加强（肌内递送）与表达由Ag 85 A、Ag 85 B和TB 10.4组成的融合蛋白的非复制型腺病毒35（rAd 35），在恒河猴（Macaca mulatta）中诱导抗原特异性细胞免疫应答的能力。对照动物接受稀释剂（3只动物）。纵向分析细胞免疫应答（每只动物12次抽血），使用细胞内细胞因子染色（TNF-α、IL-2和IFN-γ），在CD 4+、CD 8 α/β +和CD 8 α/α + T细胞亚群中测量T细胞增殖，并在7天PBMC培养物中测试IFN-γ产生使用Ag 85 A、Ag 85 B、TB10.4重组蛋白、PPD或BCG作为刺激物进行全血细胞测定（WBA）。用AFRO-1致敏的动物显示i）在WBA测定中Ag 85 B特异性IFN-γ产生增加与用BCG致敏的动物相比，用腺病毒递送的TB-抗原第一次加强后一周，（<200 pg/ml），ii）CD 8 α/α + T细胞亚群中更强的T细胞增殖（增殖指数17%），与BCG致敏的动物（CD 8 α/α + T细胞中增殖指数5%）相比。在用针对Ag 85 A/B和TB 10.4的AFRO-1致敏的2/6只动物中检测到由IFN-γ、TNF-α和IL-2产生定义的多功能T细胞;用BCG致敏的4/6只动物显示出Ag 85 A/B应答，但只有一只动物显示出Ag 85 A/B和TB 10.4反应性。与BCG相比，AFRO-1在恒河猴中诱导定性和定量不同的细胞免疫应答。在基于BCG的TB疫苗试验中，CD 8 α/α + T细胞亚群中IFN-γ应答和抗原特异性T细胞增殖的增加是疫苗接种的有价值的标志物
BCG vaccination, combined with adenoviral-delivered boosts, represents a reasonable strategy to augment, broaden and prolong immune protection against tuberculosis (TB). We tested BCG (SSI1331) (in 6 animals, delivered intradermally) and a recombinant (rBCG) AFRO-1 expressing perfringolysin (in 6 animals) followed by two boosts (delivered intramuscullary) with non-replicating adenovirus 35 (rAd35) expressing a fusion protein composed of Ag85A, Ag85B and TB10.4, for the capacity to induce antigen-specific cellular immune responses in rhesus macaques (Macaca mulatta). Control animals received diluent (3 animals). Cellular immune responses were analyzed longitudinally (12 blood draws for each animal) using intracellular cytokine staining (TNF-alpha, IL-2 and IFN-gamma), T cell proliferation was measured in CD4+, CD8alpha/beta+, and CD8alpha/alpha+ T cell subsets and IFN-gamma production was tested in 7 day PBMC cultures (whole blood cell assay, WBA) using Ag85A, Ag85B, TB10.4 recombinant proteins, PPD or BCG as stimuli. Animals primed with AFRO-1 showed i) increased Ag85B-specific IFN-gamma production in the WBA assay (median >400 pg/ml for 6 animals) one week after the first boost with adenoviral-delivered TB-antigens as compared to animals primed with BCG (<200 pg/ml), ii) stronger T cell proliferation in the CD8alpha/alpha+ T cell subset (proliferative index 17%) as compared to BCG-primed animals (proliferative index 5% in CD8alpha/alpha+ T cells). Polyfunctional T cells, defined by IFN-gamma, TNF-alpha and IL-2 production were detected in 2/6 animals primed with AFRO-1 directed against Ag85A/b and TB10.4; 4/6 animals primed with BCG showed a Ag85A/b responses, yet only a single animal exhibited Ag85A/b and TB10.4 reactivity. AFRO-1 induces qualitatively and quantitatively different cellular immune responses as compared with BCG in rhesus macaques. Increased IFN-gamma-responses and antigen-specific T cell proliferation in the CD8alpha/alpha+ T cell subset represents a valuable marker for vaccine-take in BCG-based TB vaccine trials
登录
查看更多内容
影响因子：
20.3
作者：
Konno, A;Okada, K;Koizumi, S
通讯作者：
Koizumi, S
影响因子：
3.1
作者：
Majlessi, L;Simsova, M;Leclerc, C
通讯作者：
Leclerc, C
影响因子：
3.8
作者：
Mueller, Henrik;Detjen, Anne K.;Jacobsen, Marc
通讯作者：
Jacobsen, Marc
影响因子：
4.4
作者：
Godkin, AJ;Thomas, HC;Openshaw, PJ
通讯作者：
Openshaw, PJ
影响因子：
3.9
作者：
Magalhaes, Isabelle;Vudattu, Nalini Kumar;Maeurer, Markus J.
通讯作者：
Maeurer, Markus J.