Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

ORFeome Phage Display Reveals a Major Immunogenic Epitope on the S2 Subdomain of SARS-Cov-2 Spike Protein

Rico Ballmann
* ,
Sven-Kevin Hotop
,
Federico Bertoglio
,
Stephan Steinke
ORCID logo ,
Philip Alexander Heine
,
M.-Zeeshan Chaudhry
ORCID logo ,
Dieter Jahn
,
Boas Pucker
ORCID logo ,
Fausto Baldanti
,
Antonio Piralla
ORCID logo ,
Maren Schubert
,
Luka Čičin-Šain
ORCID logo ,
Michael Hust
* ORCID logo ,
Stefan Dübel
* ORCID logo
Version 1 : Received: 20 May 2022 / Approved: 24 May 2022 / Online: 24 May 2022 (04:20:15 CEST)

A peer-reviewed article of this Preprint also exists.

Ballmann, R.; Hotop, S.-K.; Bertoglio, F.; Steinke, S.; Heine, P.A.; Chaudhry, M.Z.; Jahn, D.; Pucker, B.; Baldanti, F.; Piralla, A.; Schubert, M.; Čičin-Šain, L.; Brönstrup, M.; Hust, M.; Dübel, S. ORFeome Phage Display Reveals a Major Immunogenic Epitope on the S2 Subdomain of SARS-CoV-2 Spike Protein. Viruses 2022, 14, 1326. Ballmann, R.; Hotop, S.-K.; Bertoglio, F.; Steinke, S.; Heine, P.A.; Chaudhry, M.Z.; Jahn, D.; Pucker, B.; Baldanti, F.; Piralla, A.; Schubert, M.; Čičin-Šain, L.; Brönstrup, M.; Hust, M.; Dübel, S. ORFeome Phage Display Reveals a Major Immunogenic Epitope on the S2 Subdomain of SARS-CoV-2 Spike Protein. Viruses 2022, 14, 1326.

Abstract

The development of antibody therapies against SARS-CoV-2 remains a challenging task during the ongoing COVID-19 pandemic. All approved therapeutic antibodies are directed against the receptor binding domain (RBD) of Spike and lost neutralization efficacy against continuously emerging SARS-CoV-2 variants, which especially mutate in the RBD region. Previously, phage display has been used to identify epitopes of antibody responses against several diseases. Such epitopes have been applied to design vaccines or neutralizing antibodies. Here, we constructed an ORFeome phage display library for the SARS-CoV-2 genome. Open reading frames (ORFs) representing the SARS-CoV-2 genome were displayed on the surface of phage particles in order to identify enriched immunogenic epitopes from COVID-19 patients. Library quality was assessed by both, NGS and epitope mapping of a monoclonal antibody with known binding site. The most prominent epitope captured represented parts of Spike´s fusion peptide (FP). It is associated with the cell entry mechanism of SARS-CoV-2 into the host cell and the serine protease TMPRSS2 cleaves Spike within this sequence. Blocking of this mechanism could be a potential target for non-RBD binding therapeutic anti-SARS-CoV-2 antibodies. As mutations within the FP amino acid sequence were rather rare among SARS-CoV-2 variants so far, this may be an advantage in the fight against future virus variants.

Keywords

phage display; epitope mapping; COVID-19; genomic library; NGS

Subject

Biology and Life Sciences, Virology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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