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Nat Commun . A vaccine platform targeting lung-resident memory CD4+ T-cells provides protection against heterosubtypic influenza infections in mice

tetano

Editor, Senior Moderator
Nat Commun


. 2024 Nov 29;15(1):10368.
doi: 10.1038/s41467-024-54620-4. A vaccine platform targeting lung-resident memory CD4[SUP]+[/SUP] T-cells provides protection against heterosubtypic influenza infections in mice and ferrets

Kwang Hyun Ko[SUP] 1 2 [/SUP], Hyun Shik Bae[SUP] 1 [/SUP], Jeong Woo Park[SUP] 2 3 [/SUP], Jin-Sun Lee[SUP] 2 3 [/SUP], Somin Park[SUP] 3 [/SUP], Jun Heo[SUP] 4 [/SUP], Hyunsoo Park[SUP] 4 [/SUP], Jaeseok Choi[SUP] 5 [/SUP], Eunseo Bae[SUP] 5 [/SUP], Woonsung Na[SUP] 5 [/SUP], Seong-Hyun Park[SUP] 6 [/SUP], Baik-Lin Seong[SUP] 7 [/SUP], Seung Hyun Han[SUP] 2 3 [/SUP], Dong-Ho Kim[SUP] #[/SUP][SUP] 8 [/SUP], Seung Bin Cha[SUP] #[/SUP][SUP] 9 [/SUP]



Affiliations
Abstract

Lung tissue-resident memory T (T[SUB]RM[/SUB]) cells induced by influenza vaccination are crucial for heterosubtypic immunity upon re-exposure to the influenza virus, enabling rapid and robust responses upon reactivation. To enhance the efficacy of influenza vaccines, we induce the generation of lung T[SUB]RM[/SUB] cells following intranasal vaccination with a commercial influenza vaccine adjuvanted with NexaVant (NVT), a TLR3 agonist-based adjuvant. We demonstrate that intranasal immunization with the NVT-adjuvanted vaccine provides improved protection against influenza virus infections by inducing the generation of CD4[SUP]+[/SUP] T[SUB]RM[/SUB] cells in the lungs in a type I interferon-dependent manner. These pulmonary CD4[SUP]+[/SUP] T[SUB]RM[/SUB] cells provide potent mucosal immunity and cross-protection against heterosubtypic infections in both mouse and ferret models. This vaccine platform has the potential to significantly improve conventional intramuscular influenza vaccines by providing broader protection.


 
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