University of Minnesota
https://twin-cities.umn.edu/
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Milestone
2.6.a

Mechanisms of mucosal immunity

In progress
High priority

Characterize the role of mucosal immunity (including antibodies and T cells) in protecting against influenza virus infection, disease, and transmission.

Progress Highlights

Gailleton 2025 examined the origin and dynamics of B cell responses to influenza virus in the nasal mucosa using an upper respiratory tract-restricted infection method in a mouse model that mimics infection dynamics in humans. Results demonstrated that intranasal infection and immunization trigger a specific germinal center B cell response in the nasal turbinate which fuels the local B cell and Ab response.

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NCT06501963 Revealing Protective Immunity to Influenza Using Systems Immunology (PRISM) was initiated in 2024 to examine why the LAIV given as a nasal spray does not work as well in adults as it does in children.

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Kazer 2024 generated a single-cell RNA-sequencing atlas of the murine nasal mucosa, sampling three regions during primary influenza infection and rechallenge, and showed that influenza infection induces stepwise changes in nasal epithelial and immune subsets. 

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Kastenschmidt 2023 used a human tonsil organoid model to examine how antigen-specific B and T cells were activated and participated in adaptive immune responses within the mucosal site by tracking the differentiation and kinetics of the adaptive immune response to influenza vaccine and virus modalities; each antigen format elicited distinct B- and T-cell responses, including differences in magnitude, diversity, phenotype, function, and breadth. 

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Mahallawi 2023 used a human NALT model to evaluate local B-cell immunity induced by LAIV. Mucosal antibody responses in NALT to HAs of a number of influenza A and one influenza B viruses were investigated following in vitro stimulation of tonsillar cells with LAIV vaccine. Significant Ab responses of IgG, IgA and IgM to the HA of pH1N1 virus were observed in tonsillar cells following LAIV stimulation, suggesting that human NALT tissues are likely to be a major induction site of immune response against influenza following LAIV at the nasopharynx site. 

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Thwaites 2023 inoculated 40 healthy young adults with LAIV and performed detailed analyses of immune activation after vaccination. Results indicated the efficacy of LAIV may result from Ab responses confined to the nasal mucosa, which may provide protection not reflected by blood-based studies. 

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Rattan 2022 developed a mouse model of intranasal infection with influenza B virus and identified a series of CD4 T-cell peptide specificities to enable in depth analyses of the role of influenza B-specific CD4 T cells elicited by infection and vaccination and to assess the impact of candidate vaccines on the abundance, functionality, and localization of the elicited CD4 T cells.

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Oh 2021 used a murine model to evaluate the phenotype, residency, and role of IgA-secreting B cells in the lung and found that tissue-resident IgA-secreting B cells are the source of luminal IgA in the lung that confers sterilizing protection against challenge with homologous influenza virus and quicker recovery from heterologous challenge (preclinical study in mice).

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Paterson 2021 used a human challenge model to evaluate human lung CD8 TRM cells finding innate-like gene and protein expression between innate and adaptive immunity. 

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