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Nat Commun . Cytomegalovirus vaccine vector-induced effector memory CD4 + T cells protect cynomolgus macaques from lethal aerosolized heterologous a

tetano

Editor, Senior Moderator
Nat Commun


. 2024 Jul 19;15(1):6007.
doi: 10.1038/s41467-024-50345-6. Cytomegalovirus vaccine vector-induced effector memory CD4 + T cells protect cynomolgus macaques from lethal aerosolized heterologous avian influenza challenge

Daniel Malouli[SUP] #[/SUP][SUP] 1 [/SUP], Meenakshi Tiwary[SUP] #[/SUP][SUP] 1 [/SUP], Roxanne M Gilbride[SUP] 1 [/SUP], David W Morrow[SUP] 1 [/SUP], Colette M Hughes[SUP] 1 [/SUP], Andrea Selseth[SUP] 1 [/SUP], Toni Penney[SUP] 2 [/SUP], Priscila Castanha[SUP] 3 [/SUP], Megan Wallace[SUP] 3 [/SUP], Yulia Yeung[SUP] 3 [/SUP], Morgan Midgett[SUP] 4 [/SUP], Connor Williams[SUP] 3 [/SUP], Jason Reed[SUP] 1 [/SUP], Yun Yu[SUP] 1 [/SUP], Lina Gao[SUP] 1 [/SUP], Gabin Yun[SUP] 5 [/SUP], Luke Treaster[SUP] 5 [/SUP], Amanda Laughlin[SUP] 4 [/SUP], Jeneveve Lundy[SUP] 4 [/SUP], Jennifer Tisoncik-Go[SUP] 6 [/SUP], Leanne S Whitmore[SUP] 6 [/SUP], Pyone P Aye[SUP] 2 [/SUP], Faith Schiro[SUP] 2 [/SUP], Jason P Dufour[SUP] 2 [/SUP], Courtney R Papen[SUP] 1 [/SUP], Husam Taher[SUP] 1 [/SUP], Louis J Picker[SUP] 1 [/SUP], Klaus Früh[SUP] 1 [/SUP], Michael Gale Jr[SUP] 6 7 [/SUP], Nicholas J Maness[SUP] 2 [/SUP], Scott G Hansen[SUP] 1 [/SUP], Simon Barratt-Boyes[SUP] 8 [/SUP], Douglas S Reed[SUP] 9 [/SUP], Jonah B Sacha[SUP] 10 [/SUP]



Affiliations
Free article Abstract

An influenza vaccine approach that overcomes the problem of viral sequence diversity and provides long-lived heterosubtypic protection is urgently needed to protect against pandemic influenza viruses. Here, to determine if lung-resident effector memory T cells induced by cytomegalovirus (CMV)-vectored vaccines expressing conserved internal influenza antigens could protect against lethal influenza challenge, we immunize Mauritian cynomolgus macaques (MCM) with cynomolgus CMV (CyCMV) vaccines expressing H1N1 1918 influenza M1, NP, and PB1 antigens (CyCMV/Flu), and challenge with heterologous, aerosolized avian H5N1 influenza. All six unvaccinated MCM died by seven days post infection with acute respiratory distress, while 54.5% (6/11) CyCMV/Flu-vaccinated MCM survived. Survival correlates with the magnitude of lung-resident influenza-specific CD4 + T cells prior to challenge. These data demonstrate that CD4 + T cells targeting conserved internal influenza proteins can protect against highly pathogenic heterologous influenza challenge and support further exploration of effector memory T cell-based vaccines for universal influenza vaccine development.


 
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