RTS,S/AS01E Malaria Vaccine Induces Memory and Polyfunctional T Cell Responses in a Pediatric African Phase III Trial.
RTS,S/AS01E Malaria Vaccine Induces Memory and Polyfunctional T Cell Responses in a Pediatric African Phase III Trial.
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RTS，S/AS01E疟疾疫苗在小儿非洲III期试验中诱导记忆和多功能T细胞反应。
DOI：
10.3389/fimmu.2017.01008
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发表时间：
2017
影响因子：
7.3
通讯作者：
McElrath MJ
中科院分区：
文献类型：
--
作者：
Moncunill G;De Rosa SC;Ayestaran A;Nhabomba AJ;Mpina M;Cohen KW;Jairoce C;Rutishauser T;Campo JJ;Harezlak J;Sanz H;Díez-Padrisa N;Williams NA;Morris D;Aponte JJ;Valim C;Daubenberger C;Dobaño C;McElrath MJ
需要对RTS，S/AS 01 E疫苗的细胞应答进行全面评估，以了解潜在的相关性并最终了解预防疟疾疾病的机制。在非洲的一项儿科III期试验中，通过细胞内细胞因子染色和16色流式细胞术，对105名RTS、S/AS 01接种受试者和74名狂犬病接种受试者（对照）在初次接种前和初次接种后1个月识别RTS、含S/AS 01 E的环子孢子蛋白（CSP）和乙型肝炎B表面抗原（HBsAg）的细胞应答进行了评估。RTS、S/AS 01 E疫苗接种儿童产生IL-2、TNF-α和CD 40 L的CSP和HBsAg特异性CD 4 + T细胞以及产生IFN-γ和IL-17的HBsAg特异性CD 4 + T细胞的频率显著高于基线和对照组。在中枢和效应记忆（EM）区室中均发现了疫苗诱导的应答。检测到表达IL-4和IL-21的EM CD 4 + T细胞识别两种疫苗抗原。在RTS，S/AS 01 E疫苗接种的儿童中，观察到对两种抗原的应答率一致高于对照疫苗接种的儿童。RTS，S/AS 01 E诱导多功能CSP-和HBsAg-特异性CD 4 + T细胞，在HBsAg应答中具有更高程度的多功能性。总之，RTS，S/AS 01 E疫苗诱导的T细胞具有比先前表征的更高的功能异质性和多功能性。在记忆性CD 4 + T细胞区室中检测到的应答可能在未来的免疫相关性研究中提供RTS、S/AS 01诱导的免疫和保护持续时间的相关性。
Comprehensive assessment of cellular responses to the RTS,S/AS01E vaccine is needed to understand potential correlates and ultimately mechanisms of protection against malaria disease. Cellular responses recognizing the RTS,S/AS01E-containing circumsporozoite protein (CSP) and Hepatitis B surface antigen (HBsAg) were assessed before and 1 month after primary vaccination by intracellular cytokine staining and 16-color flow cytometry in 105 RTS,S/AS01-vaccinated and 74 rabies-vaccinated participants (controls) in a pediatric phase III trial in Africa. RTS,S/AS01E-vaccinated children had significantly higher frequencies of CSP- and HBsAg-specific CD4+ T cells producing IL-2, TNF-α, and CD40L and HBsAg-specific CD4+ T producing IFN-γ and IL-17 than baseline and the control group. Vaccine-induced responses were identified in both central and effector memory (EM) compartments. EM CD4+ T cells expressing IL-4 and IL-21 were detected recognizing both vaccine antigens. Consistently higher response rates to both antigens in RTS,S/AS01E-vaccinated than comparator-vaccinated children were observed. RTS,S/AS01E induced polyfunctional CSP- and HBsAg-specific CD4+ T cells, with a greater degree of polyfunctionality in HBsAg responses. In conclusion, RTS,S/AS01E vaccine induces T cells of higher functional heterogeneity and polyfunctionality than previously characterized. Responses detected in memory CD4+ T cell compartments may provide correlates of RTS,S/AS01-induced immunity and duration of protection in future correlates of immunity studies.
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DOI：
10.4049/jimmunol.1102710
发表时间：
2012-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Horowitz A;Hafalla JC;King E;Lusingu J;Dekker D;Leach A;Moris P;Cohen J;Vekemans J;Villafana T;Corran PH;Bejon P;Drakeley CJ;von Seidlein L;Riley EM
通讯作者：
Riley EM
影响因子：
4.3
作者：
Finak G;Frelinger J;Jiang W;Newell EW;Ramey J;Davis MM;Kalams SA;De Rosa SC;Gottardo R
通讯作者：
Gottardo R
影响因子：
2.1
作者：
Finak, Greg;McDavid, Andrew;Gottardo, Raphael
通讯作者：
Gottardo, Raphael
影响因子：
46.9
作者：
Lin L;Finak G;Ushey K;Seshadri C;Hawn TR;Frahm N;Scriba TJ;Mahomed H;Hanekom W;Bart PA;Pantaleo G;Tomaras GD;Rerks-Ngarm S;Kaewkungwal J;Nitayaphan S;Pitisuttithum P;Michael NL;Kim JH;Robb ML;O'Connell RJ;Karasavvas N;Gilbert P;C De Rosa S;McElrath MJ;Gottardo R
通讯作者：
Gottardo R
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y