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bioRxiv · 10.1101/2020.08.12.248823

Attenuated influenza virions expressing the SARS- CoV-2 receptor-binding domain induce neutralizing antibodies in mice

Loes, A. N.·Gentles, L. E.·Greaney, A. J.·Crawford, K. H.·Bloom, J. D.
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Abstract

An effective vaccine is essential to controlling the spread of SARS-CoV-2 virus. Here, we describe an influenza-virus-based vaccine for SARS-CoV-2. We incorporated a membrane-anchored form of the SARS-CoV-2 Spike receptor binding domain (RBD) in place of the neuraminidase (NA) coding sequence in an influenza virus also possessing a mutation that reduces the affinity of hemagglutinin for its sialic acid receptor. The resulting {Delta}NA(RBD)-Flu virus can be generated by reverse genetics and grown to high titers in cell culture. A single-dose intranasal inoculation of mice with {Delta}NA(RBD)-Flu elicits serum neutralizing antibody titers against SAR-CoV-2 comparable to those observed in humans following natural infection ([~]1:200). Furthermore, {Delta}NA(RBD)-Flu itself causes no apparent disease in mice. It might be possible to produce a vaccine similar to {Delta}NA(RBD)-Flu at scale by leveraging existing platforms for production of influenza vaccines.

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Loes, A. N., Gentles, L. E., Greaney, A. J., Crawford, K. H., Bloom, J. D.. 2020-08-13. Attenuated influenza virions expressing the SARS- CoV-2 receptor-binding domain induce neutralizing antibodies in mice. https://doi.org/10.1101/2020.08.12.248823

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