Cytomegalovirus vaccine vector-induced effector memory CD4 + T cells protect cynomolgus macaques from lethal aerosolized heterologous avian influenza challenge

Daniel Malouli, Meenakshi Tiwary, Roxanne M. Gilbride, David W. Morrow, Colette M. Hughes, Andrea Selseth, Toni Penney, Priscila Castanha, Megan Wallace, Yulia Yeung, Morgan Midgett, Connor Williams, Jason Reed, Yun Yu, Lina Gao, Gabin Yun, Luke Treaster, Amanda Laughlin, Jeneveve Lundy, Jennifer Tisoncik-Go, Leanne S. Whitmore, Pyone P. Aye, Faith Schiro, Jason P. Dufour, Courtney R. Papen, Husam Taher, Louis J. Picker, Klaus Früh, Michael Gale, Nicholas J. Maness, Scott G. Hansen, Simon Barratt-Boyes (), Douglas S. Reed () and Jonah B. Sacha ()
Additional contact information
Daniel Malouli: Oregon Health & Science University
Meenakshi Tiwary: Oregon Health & Science University
Roxanne M. Gilbride: Oregon Health & Science University
David W. Morrow: Oregon Health & Science University
Colette M. Hughes: Oregon Health & Science University
Andrea Selseth: Oregon Health & Science University
Toni Penney: Tulane University
Priscila Castanha: Department of Infectious Diseases and Microbiology
Megan Wallace: Department of Infectious Diseases and Microbiology
Yulia Yeung: Department of Infectious Diseases and Microbiology
Morgan Midgett: Center for Vaccine Research
Connor Williams: Department of Infectious Diseases and Microbiology
Jason Reed: Oregon Health & Science University
Yun Yu: Oregon Health & Science University
Lina Gao: Oregon Health & Science University
Gabin Yun: University of Pittsburgh
Luke Treaster: University of Pittsburgh
Amanda Laughlin: Center for Vaccine Research
Jeneveve Lundy: Center for Vaccine Research
Jennifer Tisoncik-Go: University of Washington
Leanne S. Whitmore: University of Washington
Pyone P. Aye: Tulane University
Faith Schiro: Tulane University
Jason P. Dufour: Tulane University
Courtney R. Papen: Oregon Health & Science University
Husam Taher: Oregon Health & Science University
Louis J. Picker: Oregon Health & Science University
Klaus Früh: Oregon Health & Science University
Michael Gale: University of Washington
Nicholas J. Maness: Tulane University
Scott G. Hansen: Oregon Health & Science University
Simon Barratt-Boyes: Department of Infectious Diseases and Microbiology
Douglas S. Reed: Center for Vaccine Research
Jonah B. Sacha: Oregon Health & Science University

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-50345-6

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