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

van de Ven, K.; Lanfermeijer, J.; van Dijken, H.; Muramatsu, H.; de Melo, C. V. B.; Lenz, S.; Peters, F.; Beattie, M. B.; Lin, P. J.; Ferreira, J. A.; van den Brand, J.; van Baarle, D.; Pardi, N.; de Jonge, J.

doi:10.1101/2022.08.02.502529

bioRxiv · 10.1101/2022.08.02.502529

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

van de Ven, K.·Lanfermeijer, J.·van Dijken, H.·Muramatsu, H.·de Melo, C. V. B.·Lenz, S.·Peters, F.·Beattie, M. B.·Lin, P. J.·Ferreira, J. A.·van den Brand, J.·van Baarle, D.·Pardi, N.·de Jonge, J.

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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 naive 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.

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van de Ven, K., Lanfermeijer, J., van Dijken, H., Muramatsu, H., de Melo, C. V. B., Lenz, S., Peters, F., Beattie, M. B., Lin, P. J., Ferreira, J. A., van den Brand, J., van Baarle, D., Pardi, N., de Jonge, J.. 2022-08-03. A universal influenza mRNA vaccine candidate boosts T-cell responses and reduces zoonotic influenza virus disease in ferrets. https://doi.org/10.1101/2022.08.02.502529

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