A molecular signature of lung-resident CD8 T cells elicited by subunit vaccination.

Natural infection as well as vaccination with live or attenuated viruses elicit tissue resident, CD8 memory T cell (Trm) response. Trm cells so elicited act quickly upon reencounter with the priming agent to protect the host. These Trm cells express a unique molecular signature driven by the master regulators-Runx3 and Hobit. We previously reported that intranasal instillation of a subunit vaccine in a prime boost vaccination regimen installed quick-acting, CD8 Trm cells in the lungs that protected against lethal vaccinia virus challenge. It remains unexplored whether CD8 Trm responses so elicited are driven by a similar molecular signature as those elicited by microbes in a real infection or by live, attenuated pathogens in conventional vaccination. We found that distinct molecular signatures distinguished subunit vaccine-elicited lung interstitial CD8 Trm cells from subunit vaccine-elicited CD8 effector memory and splenic memory T cells. Nonetheless, the transcriptome signature of subunit vaccine elicited CD8 Trm resembled those elicited by virus infection or vaccination. Clues to the basis of tissue residence and function of vaccine specific CD8 Trm cells were found in transcripts that code for chemokines and chemokine receptors, purinergic receptors, and adhesins when compared to CD8 effector and splenic memory T cells. Our findings inform the utility of protein-based subunit vaccination for installing CD8 Trm cells in the lungs to protect against respiratory infectious diseases that plague humankind.