英国牛津大学Paul Klenerman和Nicholas M. Provine研究组合作取得最新进展。他们揭示粘膜相关不变T（MAIT）细胞激活增强腺病毒载体疫苗的免疫原性。2021年1月29日出版的《科学》杂志发表了这项成果。
他们假设MAIT细胞在使用复制能力不佳的腺病毒载体的疫苗平台中可能具有固有的佐剂活性。 在小鼠和人类中，ChAdOx1（黑猩猩腺病毒Ox1）免疫可明显激活MAIT细胞。激活需要浆细胞样树突状细胞（pDC）来源的干扰素（IFN）-α和单核细胞来源的白介素18。IFN-α诱导的单核细胞源性肿瘤坏死因子也被确定为关键的继发信号。体内和体外都需要这三种细胞因子。
在人类志愿者中，MAIT细胞的活化与疫苗诱导的T细胞反应呈正相关，而MAIT细胞缺陷小鼠表现出对多种疫苗编码抗原的CD8 + T细胞反应受损。因此，MAIT细胞有助于腺病毒载体的免疫原性，对疫苗设计有影响。
据悉，MAIT细胞是病毒的先天传感器，可以增强早期免疫反应并有助于保护。
附：英文原文
Title: MAIT cell activation augments adenovirus vector vaccine immunogenicity
Author: Nicholas M. Provine, Ali Amini, Lucy C. Garner, Alexandra J. Spencer, Christina Dold, Claire Hutchings, Laura Silva Reyes, Michael E. B. FitzPatrick, Senthil Chinnakannan, Blanche Oguti, Meriel Raymond, Marta Ulaszewska, Fulvia Troise, Hannah Sharpe, Sophie B. Morgan, Timothy S. C. Hinks, Teresa Lambe, Stefania Capone, Antonella Folgori, Eleanor Barnes, Christine S. Rollier, Andrew J. Pollard, Paul Klenerman
Issue&Volume: 2021/01/29
Abstract: Mucosal-associated invariant T (MAIT) cells are innate sensors of viruses and can augment early immune responses and contribute to protection. We hypothesized that MAIT cells may have inherent adjuvant activity in vaccine platforms that use replication-incompetent adenovirus vectors. In mice and humans, ChAdOx1 (chimpanzee adenovirus Ox1) immunization robustly activated MAIT cells. Activation required plasmacytoid dendritic cell (pDC)–derived interferon (IFN)–α and monocyte-derived interleukin-18. IFN-α–induced, monocyte-derived tumor necrosis factor was also identified as a key secondary signal. All three cytokines were required in vitro and in vivo. Activation of MAIT cells positively correlated with vaccine-induced T cell responses in human volunteers and MAIT cell–deficient mice displayed impaired CD8+ T cell responses to multiple vaccine-encoded antigens. Thus, MAIT cells contribute to the immunogenicity of adenovirus vectors, with implications for vaccine design.
DOI: 10.1126/science.aax8819
Source: https://science.sciencemag.org/content/371/6528/521