1. A universal influenza mRNA vaccine candidate boosts T cell responses and reduces zoonotic influenza virus disease in ferrets
- Author
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van de Ven, Koen, Lanfermeijer, Josien, van Dijken, Harry, Muramatsu, Hiromi, Vilas Boas de Melo, Caroline, Lenz, Stefanie, Peters, Florence, Beattie, Mitchell B, Lin, Paulo J C, Ferreira, José A, van den Brand, Judith, van Baarle, Debbie, Pardi, Norbert, de Jonge, Jørgen, VPDC pathologie, VPDC pathologie, and Translational Immunology Groningen (TRIGR)
- Subjects
RNA, Messenger/genetics ,Multidisciplinary ,T-Lymphocytes ,Influenza A Virus, H7N9 Subtype/genetics ,H7N9 Subtype/genetics ,Influenza ,Influenza, Human/prevention & control ,Human/prevention & control ,Influenza A Virus, H1N1 Subtype ,Orthomyxoviridae Infections ,Influenza Vaccines ,Child, Preschool ,Influenza A Virus ,RNA ,Messenger/genetics ,Animals ,Humans ,H1N1 Subtype ,Ferrets/genetics ,Preschool ,Child - Abstract
Universal influenza vaccines have the potential to protect against continuously evolving and newly emerging influenza viruses. T cells may be an essential target of such vaccines as they can clear infected cells through recognition of conserved influenza virus epitopes. We evaluated a novel T cell-inducing nucleoside-modified mRNA vaccine that encodes the conserved nucleoprotein, matrix protein 1 and polymerase basic protein 1 of an H1N1 influenza virus. To mimic the human situation, we applied the mRNA vaccine as a prime-boost regimen in naïve ferrets (mimicking young children) and as a booster in influenza-experienced ferrets (mimicking adults). The vaccine induced and boosted broadly-reactive T cells in the circulation, bone marrow and respiratory tract. Booster vaccination enhanced protection against heterosubtypic infection with potential pandemic H7N9 influenza virus in influenza-experienced ferrets. Our findings show that mRNA vaccines encoding internal influenza virus proteins are a promising strategy to induce broadly-protective T-cell immunity against influenza viruses.
- Published
- 2022