Induction of tissue resident memory T cells by measles vaccine vector.

Measles live attenuated vaccine (MV) induces strong humoral and cellular systemic memory responses allowing the successful control of measles since decades. MV has also been adapted into a promising vaccine platform with several vaccine candidates in clinical development. To understand and document the tissue-scaled memory response induced by MV, we explored the specific induction and persistence of resident memory T cells (Trm) in the lungs and the liver, two critical targeted tissues for vaccine development against several diseases. Trm are a subset of non-circulating highly specialized T cells. They are found at multiple barrier and mucosal sites, conveniently positioned to rapidly react against pathogens. The induction of Trm in different tissues is therefore critical for vaccine development. We demonstrated in mice the rapid generation of MV-specific and vectorized antigen-specific Trm in the liver and the lungs after a single dose, whatever the route of immunization. The intranasal route induced more Trm in the lungs than other routes, confirming the potential of intranasal vaccine administration of replicative viral vectors to generate a strong pulmonary immune response. MV-specific Trm cells were functionally active, with CD8 ⁺ Trm secreting granzyme B upon in vitro restimulation and CD4 ⁺ Trm cells secreting IFN-γ and TNF-α. We confirmed in human lymphocytes this tissue tropism by showing an overexpression of homing receptors directing them to epithelial and inflamed tissues. Vaccination strategies able to induce Trm cells at key sites represent a promising field to improve current vaccines, prioritize vaccine platforms and design future vaccines with enhanced protective efficacy.