Статья

Route of self-amplifying mRNA vaccination modulates the establishment of pulmonary resident memory CD8 and CD4 T cells

Marco KünzliCenter for Immunology, Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USAStephen D. O’FlanaganCenter for Immunology, Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USAMadeleine LaRueCenter for Immunology, Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USAPoulami TalukderTiba Biotech LLC, Cambridge, MA, USAThamotharampillai DileepanCenter for Immunology, Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USAJ. Michael StolleyCenter for Immunology, Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USAAndrew G. SoerensCenter for Immunology, Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USAClare F. QuarnstromCenter for Immunology, Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USASathi WijeyesingheCenter for Immunology, Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USAYanqi YeEmory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USAJustine S. McPartlanTiba Biotech LLC, Cambridge, MA, USAJason S. MitchellCenter for Immunology, Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USAChristian W. MandlTiba Biotech LLC, Cambridge, MA, USARichard G. VileDepartment of Molecular Medicine, Mayo Clinic, Rochester, MN, USAMarc K. JenkinsCenter for Immunology, Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USARafi AhmedEmory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USAVaiva VezysCenter for Immunology, Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USAJasdave S. ChahalTiba Biotech LLC, Cambridge, MA, USADavid MasopustCenter for Immunology, Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USA

2022en

ABI

Аннотация

Respiratory tract resident memory T cells (T RM ), typically generated by local vaccination or infection, can accelerate control of pulmonary infections that evade neutralizing antibody. It is unknown whether mRNA vaccination establishes respiratory T RM . We generated a self-amplifying mRNA vaccine encoding the influenza A virus nucleoprotein that is encapsulated in modified dendron–based nanoparticles. Here, we report how routes of immunization in mice, including contralateral versus ipsilateral intramuscular boosts, or intravenous and intranasal routes, influenced influenza-specific cell–mediated and humoral immunity. Parabiotic surgeries revealed that intramuscular immunization was sufficient to establish CD8 T RM in the lung and draining lymph nodes. Contralateral, compared with ipsilateral, intramuscular boosting broadened the distribution of lymph node T RM and T follicular helper cells but slightly diminished resulting levels of serum antibody. Intranasal mRNA delivery established modest circulating CD8 and CD4 T cell memory but augmented distribution to the respiratory mucosa. Combining intramuscular immunizations with an intranasal mRNA boost achieved high levels of both circulating T cell memory and lung T RM . Thus, routes of mRNA vaccination influence humoral and cell-mediated immunity, and intramuscular prime-boosting establishes lung T RM that can be further expanded by an additional intranasal immunization.

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Идентификаторы

DOI: 10.1126/sciimmunol.add3075

Цитирования и источники

Цитирований: 2Использованных источников: 0

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