Priming of Memory But Not Effector CD8 T Cells by a Killed Bacterial Vaccine

TLDR

Killed or inactivated vaccines, such as heat‑killed Listeria monocytogenes, fail to elicit protective immunity despite inducing long‑lived CD8 T cell responses after live infection. Our study shows that heat‑killed Listeria immunization expands memory CD8 T cells but does not generate effector cells, demonstrating that effector T cell production is required for durable protection.

Abstract

Killed or inactivated vaccines targeting intracellular bacterial and protozoal pathogens are notoriously ineffective at generating protective immunity. For example, vaccination with heat-killed Listeria monocytogenes (HKLM) is not protective, although infection with live L. monocytogenes induces long-lived, CD8 T cell–mediated immunity. We demonstrate that HKLM immunization primes memory CD8 T lymphocyte populations that, although substantial in size, are ineffective at providing protection from subsequent L. monocytogenes infection. In contrast to live infection, which elicits large numbers of effector CD8 T cells, HKLM immunization primes T lymphocytes that do not acquire effector functions. Our studies show that it is possible to dissociate T cell–dependent protective immunity from memory T cell expansion, and that generation of effector T cells may be necessary for long-term protective immunity.