Heterosubtypic Protections against Human-Infecting Avian Influenza Viruses Correlate to Biased Cross-T-Cell Responses

Abstract

Against a backdrop of seasonal influenza virus epidemics, emerging avian influenza viruses (AIVs) occasionally jump from birds to humans, posing a public health risk, especially with the recent sharp increase in H7N9 infections. Evaluations of cross-reactive T-cell immunity to seasonal influenza viruses and human-infecting AIVs have been reported previously. However, the roles of influenza A virus-derived epitopes in the cross-reactive T-cell responses and heterosubtypic protections are not well understood; understanding those roles is important for preventing and controlling new emerging AIVs. Here, among the members of a healthy population presumed to have previously been infected by pandemic H1N1 (pH1N1), we found that pH1N1-specific T cells showed cross- but biased reactivity to human-infecting AIVs, i.e., H5N1, H6N1, H7N9, and H9N2, which correlates with distinct protections. Through a T-cell epitope-based phylogenetic analysis, the cellular immunogenic clustering expanded the relevant conclusions to a broader range of virus strains. We defined the potential key conserved epitopes required for cross-protection and revealed the molecular basis for the immunogenic variations. Our study elucidated an overall profile of cross-reactivity to AIVs and provided useful recommendations for broad-spectrum vaccine development.

Divergent Peptide Presentations of HLA-A*30 Alleles Revealed by Structures With Pathogen Peptides

“…Screening of immunogenic peptides which are presented by specific MHC I molecules is crucial for the development of vaccines for infection diseases or cancer immunotherapy and for T-cell immune response evaluation (45)(46)(47)(48)(49)(50)(51). Recently, several pre-clinical and clinical studies have shown that vaccines targeting predicted personal tumor neoantigens are feasibility, safety, and immunogenicity (45,50,(52)(53)(54)(55).…”

Identification of H1N1 influenza virus-derived T-cell epitopes and the contribution in the cross-reactivities to avian influenza virus

“…细胞免疫水平明显低于针对2009 pH1N1本身的T细胞 免疫 [12,13] . 在2009 pH1N1与多种禽流感的交叉T细胞 免疫研究中发现, 与NP相比, M1 蛋白对于不同流感亚 型的免疫原性差异贡献更大, 而这种交叉T细胞免疫反 应所产生的保护作用也在动物试验中得到了证实 [12] . 在2009 pH1N1与H7N9的M1蛋白中, 我们和国际 上其他研究组已经鉴定了一系列能够激发不同HLA超 级型个体T细胞免疫反应的保守表位 [10,13~15] .…”

“…研究表明, 2009 pH1N1 感染之所以产生相对温和临床症状, 部分是因为季节 性流感病毒感染或疫苗接种产生了交叉免疫T细胞从 而产生保护效力 [11,22] . 季节性H1和H3甲型流感病毒感 染产生的记忆性T细胞对禽流感H5N1病毒具有交叉免 疫应答 [7,20] , 并且对H7N9也能产生CD4 + 和CD8 + T细胞 交叉免疫 [12,23,24] . 新型禽流感病毒H7N9具有哺乳动物 适应性的氨基酸替换, 与其从禽类到人类的宿主转换 相关 [1,25] , 同时该病毒蛋白序列上相应的T细胞表位存 在突变, 影响了人类免疫系统识别和病毒清除 [19] .…”

“…然而, 很少有研究关注M1蛋白突变区段 表位的取代如何影响异源亚型T细胞免疫应答和流感 病毒免疫逃逸. 正如先前的结构研究所示, T细胞表位 内的氨基酸突变有助于源自不同流感病毒株的表位之 间的抗原产生差异 [12,28,29] . 在本研究中, 我们鉴定出了…”

On the Centenary of the Spanish Flu: Being Prepared for the Next Pandemic

“… 2017 ; Zhao et al . 2018 ). More efforts should be paid to the development of new drugs and its corresponding clinical assessment.…”