Moncunill Gemma, De Rosa Stephen C, Ayestaran Aintzane, Nhabomba Augusto J, Mpina Maximillian, Cohen Kristen W, Jairoce Chenjerai, Rutishauser Tobias, Campo Joseph J, Harezlak Jaroslaw, Sanz Héctor, Díez-Padrisa Núria, Williams Nana Aba, Morris Daryl, Aponte John J, Valim Clarissa, Daubenberger Claudia, Dobaño Carlota, McElrath M Juliana
ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
Front Immunol. 2017 Aug 23;8:1008. doi: 10.3389/fimmu.2017.01008. eCollection 2017.
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.
需要对细胞对RTS,S/AS01E疫苗的反应进行全面评估，以了解潜在的相关性，并最终了解预防疟疾疾病的保护机制。在非洲一项儿科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名接种RTS,S/AS01疫苗和74名接种狂犬病疫苗的参与者（对照组）在初次接种疫苗前和接种后1个月，评估了识别含RTS,S/AS01E的环子孢子蛋白（CSP）和乙型肝炎表面抗原（HBsAg）的细胞反应。接种RTS,S/AS01E疫苗的儿童产生IL-2、TNF-α和CD40L的CSP特异性和HBsAg特异性CD4 T细胞以及产生IFN-γ和IL-17的HBsAg特异性CD4 T细胞的频率显著高于基线水平和对照组。在中枢和效应记忆（EM）区室中均鉴定出疫苗诱导的反应。检测到表达IL-4和IL-21的EM CD4 T细胞识别两种疫苗抗原。观察到接种RTS,S/AS01E疫苗的儿童对两种抗原的反应率始终高于接种对照疫苗的儿童。RTS,S/AS01E诱导多功能CSP特异性和HBsAg特异性CD4 T细胞，HBsAg反应中的多功能程度更高。总之，RTS,S/AS01E疫苗诱导的T细胞功能异质性和多功能性高于先前的特征描述。在记忆CD4 T细胞区室中检测到的反应可能为未来免疫相关性研究中RTS,S/AS01诱导的免疫和保护持续时间提供相关性。
