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bioRxiv · 10.1101/2020.12.22.423965

Development of a novel hybrid alphavirus-SARS-CoV-2 particle for rapid in vitro screening and quantification of neutralization antibodies, antiviral drugs, and viral mutations

Hetrick, B.·He, S.·Chilin, L. D.·Dabbagh, D.·Alem, F.·Narayanan, A.·Luchini, A.·Li, T.·Liu, X.·Liotta, L.·Wu, Y.
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Abstract

Timely development of vaccines and antiviral drugs is critical to control the COVID-19 pandemic 1-6. Current methods for quantifying vaccine-induced neutralizing antibodies involve the use of pseudoviruses, such as the SARS-CoV-2 spike protein (S) pseudotyped lentivirus7-14. However, these pseudoviruses contain structural proteins foreign to SARS-CoV-2, and require days to infect and express reporter genes15. Here we describe the development of a new hybrid alphavirus-SARS-CoV-2 (Ha-CoV-2) particle for rapid and accurate quantification of neutralization antibodies and viral variants. Ha-CoV-2 is a non-replicating SARS-CoV-2 virus-like particle, composed of SARS-CoV-2 structural proteins (S, M, N, and E) and a RNA genome derived from a fast expressing alphavirus vector 16. We demonstrated that Ha-CoV-2 can rapidly and robustly express reporter genes in target cells within 3-6 hours. We further validated Ha-CoV-2 for rapid quantification of neutralization antibodies, viral variants, and antiviral drugs. In addition, as a proof-of-concept, we assembled and compared the relative infectivity of a panel of 10 Ha-CoV-2 variant isolates (D614G, P.1, B.1.1.207, B.1.351, B.1.1.7, B.1.429, B.1.258, B.1.494, B.1.2, B.1.1298), and demonstrated that these variants in general are 2-10 fold more infectious. Furthermore, we quantified the anti-serum from an infected and vaccinated individual; the one dose vaccination with Moderna mRNA-1273 has greatly increased the anti-serum titer for approximately 6 fold. The post-vaccination serum has also demonstrated various neutralizing activities against all 9 variants tested. These results demonstrated that Ha-CoV-2 can be used as a robust platform for rapid quantification of neutralizing antibodies against SARS-CoV-2 and its variants.

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Hetrick, B., He, S., Chilin, L. D., Dabbagh, D., Alem, F., Narayanan, A., Luchini, A., Li, T., Liu, X., Liotta, L., Wu, Y.. 2020-12-23. Development of a novel hybrid alphavirus-SARS-CoV-2 particle for rapid in vitro screening and quantification of neutralization antibodies, antiviral drugs, and viral mutations. https://doi.org/10.1101/2020.12.22.423965

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