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

• Published in: Frontiers in immunology Vol. 14; p. 1043631
• Main 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
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 14.02.2023
• Subjects: Animals; CD8 T cells; CD8-Positive T-Lymphocytes - immunology; Cell Division; Immunization, Secondary; Immunological Memory Cells - immunology; Immunology; memory; Mice; Mice, Inbred BALB C; prime-boost interval; transcriptomic profile; Vaccination; Vaccines; memory; prime-boost interval; transcriptomic profile; CD8 T cells; vaccination
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1043631

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 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.