Induction of tissue resident memory T cells by measles vaccine vector
Heidy Vera-Peralta1,2, Claude Ruffié1, Valérie Najburg1
1Institut Pasteur-Oncovita Joint Laboratory, Université Paris Cité, Institut Pasteur, Paris, France.
Abstract:
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.
Insights
Measles live attenuated vaccine (MV) rapidly generates tissue-specific memory T cells (Trm) in the lungs and liver. This finding supports MV as a vaccine platform for enhanced immune protection.
Area of Science:
- Immunology
- Vaccinology
- Cellular Biology
Background:
- Measles live attenuated vaccine (MV) effectively controls measles via systemic immune memory.
- MV serves as a versatile platform for developing new vaccines.
- Understanding tissue-specific memory responses is crucial for vaccine design.
Purpose of the Study:
- To investigate the induction and persistence of resident memory T cells (Trm) in the lungs and liver following MV vaccination.
- To evaluate the impact of different immunization routes on Trm generation.
- To assess the functional activity of MV-induced Trm.
Main Methods:
- Mice were immunized with MV, and MV-specific Trm were analyzed in lung and liver tissues.
- Different immunization routes (including intranasal) were compared for their efficacy in inducing Trm.
- Functional assays were performed on CD8+ and CD4+ Trm to assess effector functions.
- Human lymphocytes were analyzed for homing receptor expression to confirm tissue tropism.
Main Results:
- A single dose of MV rapidly induced MV-specific Trm in both the liver and lungs, irrespective of administration route.
- Intranasal immunization resulted in a higher number of Trm in the lungs compared to other routes.
- MV-specific Trm exhibited functional activity, with CD8+ Trm secreting granzyme B and CD4+ Trm secreting IFN-γ and TNF-α.
- Human lymphocytes showed overexpression of homing receptors, indicating tissue tropism for inflamed and epithelial sites.
Conclusions:
- MV vaccination effectively generates functional Trm in key tissues like the lungs and liver.
- The intranasal route shows promise for inducing robust pulmonary immune responses.
- Inducing Trm at specific tissue sites is a promising strategy for improving vaccine efficacy and platform selection.
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