Frontiers in Immunology (Feb 2023)

Improved memory CD8 T cell response to delayed vaccine boost is associated with a distinct molecular signature

  • Ambra Natalini,
  • Sonia Simonetti,
  • Gabriele Favaretto,
  • Lorenzo Lucantonio,
  • Lorenzo Lucantonio,
  • Giovanna Peruzzi,
  • Miguel Muñoz-Ruiz,
  • Gavin Kelly,
  • Alessandra M. Contino,
  • Roberta Sbrocchi,
  • Simone Battella,
  • Stefania Capone,
  • Antonella Folgori,
  • Alfredo Nicosia,
  • Alfredo Nicosia,
  • Angela Santoni,
  • Adrian C. Hayday,
  • Adrian C. Hayday,
  • Adrian C. Hayday,
  • Francesca Di Rosa

Journal volume & issue
Vol. 14


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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 post-prime, 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.