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Review 1: "A Targeted Vaccine against COVID-19: S1-Fc Vaccine Targeting the Antigen-Presenting Cell Compartment Elicits Protection against SARS-CoV-2 Infection"

Study claims the S1-Fc vaccine provides protective activity against COVID-19 live infection. Given the urgent need for a vaccine, this data is worth publishing but the study has some defects, including the need for controls to enhance the quality of the study.

Published onAug 11, 2020
Review 1: "A Targeted Vaccine against COVID-19: S1-Fc Vaccine Targeting the Antigen-Presenting Cell Compartment Elicits Protection against SARS-CoV-2 Infection"
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key-enterThis Pub is a Review of
A Targeted Vaccine against COVID-19: S1-Fc Vaccine Targeting the Antigen-Presenting Cell Compartment Elicits Protection against SARS-CoV-2 Infection
A Targeted Vaccine against COVID-19: S1-Fc Vaccine Targeting the Antigen-Presenting Cell Compartment Elicits Protection against SARS-CoV-2 Infection
Description

Vaccination efficacy is enhanced by targeting the antigen-presenting cell compartment. Here, we show that S1-Fc antigen delivery targeting the FcgammaR+ 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 FcgammaR+ antigen-presenting cells. Immediately upon administration intramuscularly, our novel vaccine candidate recombinant rS1-Fc homes to lymph nodes in vivo where FcgammaR+ 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.

This manuscript focuses on developing a vaccine for SARS COV-2. The authors develop an Fc-fused antigen of the S1 domain of SARS COV-2, which is designed to target antigen to Fc-gamma-R+ APCs. The antigen is delivered as both a plasmid and as recombinant protein.

Several biochemical assays were performed to demonstrate that the Fc-S1 fusion protein was expressed properly and was able to bind the Ace2 receptor. Animal experiments are presented that demonstrate that the Fc-S1 antigen, in the protein format, can elicit antibodies and that these antibodies can inhibit viral replication in cells.

The Fc-S1 fused antigen strategy seems promising, and given the urgent need for a vaccine, this data is worth publishing.

A few controls would enhance the quality of the paper.


(1) Immunization with just the S1 protein is necessary to determine the impact and significance of the Fc fusion


(2) The viral inhibition assay needs additional verification, RT-PCR on the virus treated cells should be done to verify that viral inhibition has actually occurred.


(3) There are currently several other SARS COV-2 vaccines being developed, it would be very helpful to have a side by side comparison against an mRNA vaccine or an attenuated viral vaccine.

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