State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China.
Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, Hubei International Scientific and Technological Cooperation Base of Pesticide and Green Synthesis, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan, Hubei 430079, PR China.
ACS Infect Dis. 2022 Oct 14;8(10):2161-2170. doi: 10.1021/acsinfecdis.2c00296. Epub 2022 Aug 31.
Adjuvants are essential components of vaccines. Invariant natural killer T (iNKT) cells are a distinct subset of T cells that function to bridge the innate and adaptive immunities and are capable of mediating strong and rapid responses to a range of diseases, including cancer and infectious disease. An increasing amount of evidence suggests that iNKT cells can help fight viral infection. In particular, iNKT-secreting IL-4 is a key mediator of humoral immunity and has a positive correlation with the levels of neutralizing antibodies. As iNKT cell agonists, αGC glycolipid (α-galactosylceramide, or KRN7000) and its analogues as vaccine adjuvants have begun to provide vaccinologists with a new toolset. Herein we found that a new iNKT-cell agonist αGC-CPOEt elicited a strong cytokine response with increased IL-4 production. Remarkably, after three immunizations, SARS-CoV-2 RBD-Fc adjuvanted by αGC-CPOEt evoked robust neutralizing antibody responses that were about 5.5-fold more than those induced by αGC/RBD-Fc and 25-fold greater than those induced by unadjuvanted RBD-Fc. These findings imply that αGC-CPOEt could be investigated further as a new COVID-19 vaccine adjuvant to prevent current and future infectious disease outbreaks.
佐剂是疫苗的重要组成部分。不变自然杀伤 T(iNKT)细胞是 T 细胞的一个独特亚群，其功能是连接先天免疫和适应性免疫，并能够对一系列疾病(包括癌症和传染病)产生强烈和快速的反应。越来越多的证据表明，iNKT 细胞可以帮助抵抗病毒感染。特别是，iNKT 分泌的 IL-4 是体液免疫的关键介质，与中和抗体水平呈正相关。作为 iNKT 细胞激动剂，αGC 糖脂(α-半乳糖基神经酰胺，或 KRN7000)及其类似物作为疫苗佐剂，已开始为疫苗学家提供一种新的工具。在这里，我们发现一种新型 iNKT 细胞激动剂 αGC-CPOEt 引起强烈的细胞因子反应，增加了 IL-4 的产生。值得注意的是，经过三次免疫接种，αGC-CPOEt 佐剂的 SARS-CoV-2 RBD-Fc 引发了强烈的中和抗体反应，比 αGC/RBD-Fc 诱导的反应高约 5.5 倍，比未佐剂的 RBD-Fc 高 25 倍。这些发现意味着 αGC-CPOEt 可以作为一种新的 COVID-19 疫苗佐剂进一步研究，以预防当前和未来的传染病爆发。
