Examination of Influenza Specific T Cell Responses after Influenza Virus Challenge in Individuals Vaccinated with MVA-NP+M1 Vaccine

Current influenza vaccines stimulate neutralising antibody to the haemagglutinin antigen but as there is antigenic drift in HA it is difficult to prepare a vaccine in advance against an emergent strain. A potential strategy is to induce CD8+ and CD4+ T cells that recognize epitopes within internal proteins that are less subject to antigenic drift. Augmenting humoral responses to HA with T cell responses to more conserved antigens may result in a more broadly protective vaccine. In this study, we evaluate the quality of influenza specific T cell responses in a clinical trial using MVA-NP+M1 vaccination followed by influenza virus challenge. In vaccinated volunteers, the expression of Granzyme A, Perforin and CD57 on influenza HLA A*02 M158–66 antigen specific cells was higher than non-vaccinated volunteers before and after challenge despite a similar frequency of antigen specific cells. BCL2 expression was lower in vaccinated volunteers. These data indicate that antigen specific T cells are a useful additional measure for use in human vaccination or immunization studies.

当前流感疫苗可诱导针对血凝素（haemagglutinin, HA）抗原的中和抗体，但由于HA存在抗原漂移（antigenic drift），难以提前制备针对新发毒株的疫苗。一种潜在策略是诱导识别内部蛋白表位的CD8阳性T细胞（CD8+ T cells）与CD4阳性T细胞（CD4+ T cells），此类内部蛋白受抗原漂移的影响相对更小。借助针对更保守抗原（conserved antigens）的T细胞应答来增强针对HA的体液免疫应答（humoral responses），或可开发出广谱保护性疫苗（broadly protective vaccine）。本研究在一项临床试验（clinical trial）中评估了接种MVA-NP+M1疫苗后再实施流感病毒攻毒的受试者体内流感特异性T细胞应答的质量。结果显示，尽管抗原特异性细胞的频率相似，但在攻毒前后，接种疫苗受试者体内流感人类白细胞抗原A*02（HLA A*02）限制性M158–66抗原特异性细胞中，颗粒酶A（Granzyme A）、穿孔素（Perforin）与CD57的表达水平均高于未接种受试者；而接种受试者体内的B细胞淋巴瘤2（BCL2）表达水平更低。上述数据表明，抗原特异性T细胞可作为人类疫苗接种或免疫研究中一项有效的补充检测指标。