Pivotal role of tissue-resident memory lymphocytes in the control of mucosal infections: can mucosal vaccination induce protective tissue-resident memory T and B cells?

Vaccines able to induce long-term mucosal responses are needed to improve protection against infection at mucosal surfaces. Expanding polyfunctional and cross-reactive tissue-resident memory responses using mucosal vaccination on its own or combined to systemic vaccination looks a promising way to reach this goal. An ideal vaccine would induce controlled and balanced Trm and/or Brm responses at mucosal sites. For this purpose, a better knowledge is needed to understand the formation of effective tissue-resident memory responses at mucosal surfaces and to determine the specific environment needed in each mucosal tissue to generate protective Trm and Brm subsets. Identifying effective mucosal adjuvants able to induce mucosal tissue-resident memory responses is a key parameter to optimize vaccine formulations. However, it will be challenging to move vaccine candidates into clinical trials if there are not any standard procedures to quantify Trm and Brm responses in human mucosal tissues. Identification of peripheral markers correlating with Trm and/or Brm responses could be an easy way to evaluate mucosal tissue-resident memory responses post-vaccination in humans.