Gilfillan, Connie BConnie BGilfillanWang, ChensuChensuWangMohsen, Mona Omar MahmoudMona Omar MahmoudMohsenRufer, NathalieNathalieRuferHebeisen, MichaelMichaelHebeisenAllard, MathildeMathildeAllardVerdeil, GrégoryGrégoryVerdeilIrvine, Darrell JDarrell JIrvineBachmann, MartinMartinBachmannSpeiser, Daniel EDaniel ESpeiser2024-10-282024-10-282020-04https://boris-portal.unibe.ch/handle/20.500.12422/184607It 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.enAvidity regulation Functional avidity Prime/boost T-cell receptor affinity T-cell vaccination600 - Technology::610 - Medicine & healtharticle10.7892/boris.1370143178515310.1002/eji.201948355