Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, MN, 55905, USA.
Sci Rep. 2024 Aug 13;14(1):18776. doi: 10.1038/s41598-024-69825-2.
Although neutralizing antibody is an established correlate of protection for measles, T cell-mediated responses play at least two critical roles in immunity to measles: first, through provision of 'help' enabling robust humoral immune responses; and second, through clearance of measles virus-infected cells. Previously, we identified 13 measles-derived peptides that bound to human leukocyte antigen (HLA) molecules in Priess cells infected with measles virus. In this study, we evaluated the immunogenicity of these peptides in a transgenic mouse model. Our results demonstrated that these peptides induced Th1-biased immune responses at varying levels. Of the 13 peptides, the top four immunogenic peptides were further selected for a viral challenge study in mice. A vaccine based on a combination of these four peptides reduced morbidity and weight loss after viral challenge compared to placebo. Our results emphasize the potential of T cell-mediated, peptide-based vaccines against measles.
虽然中和抗体是麻疹保护的既定相关物,但 T 细胞介导的反应在麻疹免疫中至少发挥两个关键作用:首先,通过提供“帮助”,使体液免疫反应增强;其次,通过清除麻疹病毒感染的细胞。此前,我们鉴定了 13 种与麻疹病毒感染的 Priess 细胞中人类白细胞抗原 (HLA) 分子结合的麻疹衍生肽。在这项研究中,我们在转基因小鼠模型中评估了这些肽的免疫原性。我们的结果表明,这些肽以不同水平诱导了 Th1 偏向的免疫反应。在这 13 种肽中,前 4 种免疫原性肽被进一步选择用于小鼠的病毒挑战研究。与安慰剂相比,基于这四种肽的组合的疫苗可降低病毒攻击后的发病率和体重减轻。我们的结果强调了 T 细胞介导的、基于肽的麻疹疫苗的潜力。