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A universal influenza mRNA vaccine candidate boosts T cell responses and reduces zoonotic influenza virus disease in ferrets - Science Virology

Mary Wilson

Well-known member
14 Dec 2022

DOI: 10.1126/sciadv.adc9937

KOEN VAN DE VEN, JOSIEN LANFERMEIJER, HARRY VAN DIJKEN, HIROMI MURAMATSU, CAROLINE VILAS BOAS DE MELO, STEFANIE LENZ, FLORENCE PETERS, MITCHELL B. BEATTIE, PAULO J. C. LIN, JOSÉ A. FERREIRA, JUDITH VAN DEN BRAND, DEBBIE VAN BAARLE, NORBERT PARDI, AND JØRGEN DE JONGE

Abstract

Universal influenza vaccines should 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 messenger RNA (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 a potential pandemic H7N9 influenza virus in influenza-experienced ferrets. Our findings show that mRNA vaccines encoding internal influenza virus proteins represent a promising strategy to induce broadly protective T cell immunity against influenza viruses.

https://www.science.org/doi/10.1126/sciadv.adc9937
 
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