MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
PLoS One. 2013 May 3;8(5):e62778. doi: 10.1371/journal.pone.0062778. Print 2013.
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.
目前的流感疫苗能刺激针对血凝素抗原的中和抗体，但由于 HA 存在抗原漂移，因此很难提前针对新出现的菌株制备疫苗。一种潜在的策略是诱导识别内部蛋白中表位的 CD8(+)和 CD4(+)T 细胞，这些表位较少受到抗原漂移的影响。用针对更保守抗原的 T 细胞反应增强对 HA 的体液反应可能会产生更广泛的保护疫苗。在这项研究中，我们使用 MVA-NP+M1 疫苗接种后进行流感病毒挑战，在临床试验中评估流感特异性 T 细胞反应的质量。在接种疫苗的志愿者中，尽管在挑战前后针对流感 HLA A*02 M158-66 抗原的特异性细胞的频率相似，但 Granzyme A、穿孔素和 CD57 在表达上高于未接种疫苗的志愿者。BCL2 的表达在接种疫苗的志愿者中较低。这些数据表明，抗原特异性 T 细胞是用于人类接种或免疫研究的有用的附加测量指标。
