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- Title
Improved memory CD8 T cell response to delayed vaccine boost is associated with a distinct molecular signature.
- Authors
Natalini, Ambra; Simonetti, Sonia; Favaretto, Gabriele; Lucantonio, Lorenzo; Peruzzi, Giovanna; Muñoz-Ruiz, Miguel; Kelly, Gavin; Contino, Alessandra M.; Sbrocchi, Roberta; Battella, Simone; Capone, Stefania; Folgori, Antonella; Nicosia, Alfredo; Santoni, Angela; Hayday, Adrian C.; Di Rosa, Francesca
- Abstract
Effective secondary response to antigen is a hallmark of immunological memory. However, the extent of memory CD8 T cell response to secondary boost varies at different times after a primary response. Considering the central role of memory CD8 T cells in long-lived protection against viral infections and tumors, a better understanding of the molecular mechanisms underlying the changing responsiveness of these cells to antigenic challenge would be beneficial. We examined here primed CD8 T cell response to boost in a BALB/c mouse model of intramuscular vaccination by priming with HIV-1 gag-encoding Chimpanzee adenovector, and boosting with HIV-1 gag-encoding Modified Vaccinia virus Ankara. We found that boost was more effective at day(d)100 than at d30 postprime, as evaluated at d45 post-boost by multi-lymphoid organ assessment of gag-specific CD8 T cell frequency, CD62L-expression (as a guide to memory status) and in vivo killing. RNA-sequencing of splenic gag-primed CD8 T cells at d100 revealed a quiescent, but highly responsive signature, that trended toward a central memory (CD62L+) phenotype. Interestingly, gag-specific CD8 T cell frequency selectively diminished in the blood at d100, relative to the spleen, lymph nodes and bone marrow. These results open the possibility to modify prime/ boost intervals to achieve an improved memory CD8 T cell secondary response.
- Subjects
IMMUNOLOGIC memory; VACCINE effectiveness; T cells; VACCINIA; VIRUS diseases
- Publication
Frontiers in Immunology, 2023, Vol 14, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2023.1043631