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

Abstract

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.

PLGA micro/nanoparticle vaccination elicits non-tumor antigen specific resident memory CD8+ T cell protection from hepatocellular carcinoma

“…14 Increasing studies find the intra-tumoral HBV-specific CD103 + CD69 + CD8 + TRMs correlated with the improved prognosis of HBV + HCC patients. Furthermore, the degree of infiltration of CD8 + TRMs is associated with good prognosis of malignant tumors such as lung cancer 15 and melanoma. 16 Thus, a feasible immune intervention therapy approach is to reverse the immune microenvironment by targeting the activation of the non-tumor specific CD8 + TRMs, and then further improving the tumor-specific T cells to activate and proliferate through the crosstalk between cytokines or chemical factors among immune cells.…”

Advances in vaccines: revolutionizing disease prevention

“…The results suggest that the ZIKV envelope glycoprotein is highly immunogenic and could be a potential target for developing a vaccine against ZIKV. A paper by Suryadevara et al 13 contributes to understanding the molecular signature of CD8 + Trm cells elicited by subunit vaccination and their potential to protect against respiratory infectious diseases. The molecular signature of subunit vaccine-elicited CD8 + Trm cells resembles those elicited by virus infection or vaccination, with distinct molecular signatures distinguishing lung interstitial CD8 + Trm cells from effector memory and splenic memory counterparts.…”