Defining mRNA-generated T cell memory in respiratory viral infection

Abstract

T cell immune memory provides protective effector mechanisms to restrict pathogen growth upon secondary infection, although the ability of T cells generated by novel mRNA-LNP vaccines to restrict viral infection in currently unknown. To address this, we studied antigen specific T cell memory generated by mRNA-LNP vaccines in both humans and mice. We report that functional and durable T cell memory is induced by mRNA vaccines in humans, and we define functional T cell correlates of so-called ‘hybrid immunity’ through the study of T cell cytokine production in human blood. Further, we report that mRNA-LNP immunization of mice provides incomplete benefits when compared to previous infection and unexposed naïve mice challenged with influenza virus in the absence of neutralizing antibodies. This intermediate state of protection was associated with a lack of resident memory cells following initial vaccination but expeditated T cell recruitment and adaptation to the lung when compared to unexposed mice. Together, our data imply that mRNA-LNP vaccine-generated memory T cells can provide limited protective capacity in the absence of neutralizing antibodies, but this protective benefit could be substantially improved by adapting aspects of previous infection in future vaccine regimens.