It is known that for achieving high affinity antibody responses, vaccines must be optimized for antigen dose/density, and the prime/boost interval should be at least 4 weeks. Similar knowledge is lacking for generating high avidity T-cell responses. The functional avidity (FA) of T cells, describing responsiveness to peptide, is associated with the quality of effector function and the protective capacity in vivo. Despite its importance, the FA is rarely determined in T-cell vaccination studies. We addressed the question whether different time intervals for short-term homologous vaccinations impact the FA of CD8 T-cell responses. Four-week instead of 2-week intervals between priming and boosting with potent subunit vaccines in C57BL/6 mice did not improve FA. Equally, similar FA was observed after vaccination with virus-like particles displaying low versus high antigen densities. Interestingly, FA was stable in vivo but not in vitro, depending on the antigen dose and the time interval since T-cell activation, as observed in murine monoclonal T cells. Our findings suggest dynamic in vivo modulation for equal FA. We conclude that low antigen density vaccines or a minimal 4-week prime/boost interval are not crucial for the T-cell's FA, in contrast to antibody responses.

中文翻译：

---

鼠CD8 T细胞功能性亲和力在体内是稳定的，但在体外却不是：与同源的初免/加强时间间隔和抗原密度无关。

众所周知，为了获得高亲和力的抗体反应，必须针对抗原的剂量/密度优化疫苗，初免/加强间隔至少应为4周。缺乏产生高亲和力T细胞反应的类似知识。T细胞的功能性亲和力（FA）描述了对肽的反应性，与效应子功能的质量和体内的保护能力有关。尽管它很重要，但在T细胞疫苗接种研究中很少确定FA。我们提出了一个问题，即短期同源疫苗接种的不同时间间隔是否会影响CD8 T细胞反应的FA。在C57BL / 6小鼠中，初次接种和加强接种亚单位疫苗之间的间隔为4周而不是2周，这并没有改善FA。一样，用显示低密度与高密度抗原的病毒样颗粒接种疫苗后，观察到相似的FA。有趣的是，如在鼠单克隆T细胞中所观察到的，FA根据抗原剂量和自T细胞活化以来的时间间隔在体内是稳定的，但在体外不是稳定的。我们的研究结果表明动态体内调制相等的FA。我们得出结论，与抗体应答相反，低抗原密度疫苗或最小的4周初次/加强间隔对T细胞的FA至关重要。