A Targeted Vaccine against COVID-19: S1-Fc Vaccine Targeting the Antigen-Presenting Cell Compartment Elicits Protection against SARS-CoV-2 Infection

Herrmann, A.; Maruyama, J.; Yue, C.; Lahtz, C.; Zhou, H.; Kerwin, L.; Guo, W.; Zhang, Y.; Soo Hoo, W.; Yei, S.; Kwon, S.; Fu, Y.; Johnson, S.; Ledesma, A.; Zhuang, Y.; Yei, E.; Adamus, T.; Praessler, S.; Ji, H.

doi:10.1101/2020.06.29.178616

bioRxiv · 10.1101/2020.06.29.178616

A Targeted Vaccine against COVID-19: S1-Fc Vaccine Targeting the Antigen-Presenting Cell Compartment Elicits Protection against SARS-CoV-2 Infection

Herrmann, A.·Maruyama, J.·Yue, C.·Lahtz, C.·Zhou, H.·Kerwin, L.·Guo, W.·Zhang, Y.·Soo Hoo, W.·Yei, S.·Kwon, S.·Fu, Y.·Johnson, S.·Ledesma, A.·Zhuang, Y.·Yei, E.·Adamus, T.·Praessler, S.·Ji, H.

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Abstract

Vaccination efficacy is enhanced by targeting the antigen-presenting cell compartment. Here, we show that S1-Fc antigen delivery targeting the Fc{gamma}R+ antigen-presenting cell compartment elicits anti-SARS-CoV-2 S1-antigen specific IgG production in vivo exerting biologically functional and protective activity against live virus infection, assessed in a stringent experimental virus challenge assay in vitro. The S1-domain of the SARS-CoV-2 spike protein was genetically fused to a human immunoglobulin Fc moiety, which contributes to mediate S1-Fc cellular internalization by Fc{gamma}R+ antigen-presenting cells. Immediately upon administration intramuscularly, our novel vaccine candidate recombinant rS1-Fc homes to lymph nodes in vivo where Fc{gamma}R+ antigen-presenting cells reside. Seroconversion is achieved as early as day 7, mounting considerably increased levels of anti-S1 IgGs in vivo. Interestingly, immunization at elevated doses with non-expiring S1-Fc encoding dsDNA favors the education of a desired antigen-specific adaptive T cell response. However, low-dose immunization, safeguarding patient safety, using recombinant rS1-Fc, elicits a considerably elevated protection amplitude against live SARS-CoV-2 infection. Our promising findings on rS1-Fc protein immunization prompted us to further develop an affordable and safe product for delivery to our communities in need for COVID-19 vaccinations.

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Herrmann, A., Maruyama, J., Yue, C., Lahtz, C., Zhou, H., Kerwin, L., Guo, W., Zhang, Y., Soo Hoo, W., Yei, S., Kwon, S., Fu, Y., Johnson, S., Ledesma, A., Zhuang, Y., Yei, E., Adamus, T., Praessler, S., Ji, H.. 2020-06-30. A Targeted Vaccine against COVID-19: S1-Fc Vaccine Targeting the Antigen-Presenting Cell Compartment Elicits Protection against SARS-CoV-2 Infection. https://doi.org/10.1101/2020.06.29.178616

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