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A synthetic peptide CTL vaccine targeting nucleocapsid confers protection from SARS-CoV-2 challenge in rhesus macaques

View ORCID ProfilePaul E. Harris, Trevor Brasel, Christopher Massey, C. V. Herst, Scott Burkholz, Peter Lloyd, Tikoes Blankenberg, Thomas M. Bey, Richard Carback, Thomas Hodge, Serban Ciotlos, Lu Wang, Jason E. Comer, Reid Rubsamen
doi: https://doi.org/10.1101/2021.04.24.441228
Paul E. Harris
1Department of Medicine, Columbia University, P&S 10-502, 650 West 168th Street, New York, NY, USA 10032; .
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  • For correspondence: peh1@cumc.columbia.edu
Trevor Brasel
2Department of Microbiology & Immunology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX, 77555, USA; (T.Br.); (J.C.); (C.M.)
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  • For correspondence: trbrasel@utmb.edu jscomer@utmb.edu chmassey@utmb.edu
Christopher Massey
2Department of Microbiology & Immunology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX, 77555, USA; (T.Br.); (J.C.); (C.M.)
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C. V. Herst
3Flow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, 94523, USA; (C.H.); (S.B.); (R.C.); (T.H.); (S.C.); (L.W.); (P.L.), (R.R.)
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Scott Burkholz
3Flow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, 94523, USA; (C.H.); (S.B.); (R.C.); (T.H.); (S.C.); (L.W.); (P.L.), (R.R.)
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Peter Lloyd
3Flow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, 94523, USA; (C.H.); (S.B.); (R.C.); (T.H.); (S.C.); (L.W.); (P.L.), (R.R.)
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Tikoes Blankenberg
3Flow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, 94523, USA; (C.H.); (S.B.); (R.C.); (T.H.); (S.C.); (L.W.); (P.L.), (R.R.)
4Dignity Health Mercy Medical Center, Redding, CA, USA, 96001; (T.Be.); (T.Bl.)
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Thomas M. Bey
4Dignity Health Mercy Medical Center, Redding, CA, USA, 96001; (T.Be.); (T.Bl.)
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Richard Carback
3Flow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, 94523, USA; (C.H.); (S.B.); (R.C.); (T.H.); (S.C.); (L.W.); (P.L.), (R.R.)
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Thomas Hodge
3Flow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, 94523, USA; (C.H.); (S.B.); (R.C.); (T.H.); (S.C.); (L.W.); (P.L.), (R.R.)
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Serban Ciotlos
3Flow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, 94523, USA; (C.H.); (S.B.); (R.C.); (T.H.); (S.C.); (L.W.); (P.L.), (R.R.)
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Lu Wang
3Flow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, 94523, USA; (C.H.); (S.B.); (R.C.); (T.H.); (S.C.); (L.W.); (P.L.), (R.R.)
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Jason E. Comer
2Department of Microbiology & Immunology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX, 77555, USA; (T.Br.); (J.C.); (C.M.)
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  • For correspondence: reid.rubsamen@UHHospitals.org jscomer@utmb.edu trbrasel@utmb.edu jscomer@utmb.edu chmassey@utmb.edu
Reid Rubsamen
3Flow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, 94523, USA; (C.H.); (S.B.); (R.C.); (T.H.); (S.C.); (L.W.); (P.L.), (R.R.)
5The Department of Anesthesiology and Perioperative Medicine, University Hospitals, Cleveland Medical Center, Case Western Reserve School of Medicine, Cleveland, OH, USA;
6Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA 02114.
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  • For correspondence: reid.rubsamen@UHHospitals.org jscomer@utmb.edu cvherst@flowpharma.com sburkholz@flowpharma.com rcarback@flowpharma.com thodge@flowpharma.com sciotlos@flowpharma.com lwang@flowpharma.com plloyd@flowpharma.com rrubsamen@flowpharma.com reid.rubsamen@uhhospitals.org
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Abstract

Background Persistent transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has given rise to a COVID-19 pandemic. Several vaccines, evoking protective spike antibody responses, conceived in 2020, are being deployed in mass public health vaccination programs. Recent data suggests, however, that as sequence variation in the spike genome accumulates, some vaccines may lose efficacy.

Methods Using a macaque model of SARS-CoV-2 infection, we tested the efficacy of a peptide-based vaccine targeting MHC Class I epitopes on the SARS-CoV-2 nucleocapsid protein. We administered biodegradable microspheres with synthetic peptides and adjuvants to rhesus macaques. Unvaccinated control and vaccinated macaques were challenged with 1 x 108 TCID50 units of SARS-CoV-2, followed by assessment of clinical symptoms, viral load, chest radiographs, sampling of peripheral blood and bronchoalveolar lavage (BAL) fluid for downstream analysis.

Results Vaccinated animals were free of pneumonia-like infiltrates characteristic of SARS-CoV-2 infection and presented with lower viral loads relative to controls. Gene expression in cells collected from BAL samples of vaccinated macaques revealed a unique signature associated with enhanced development of adaptive immune responses relative to control macaques.

Conclusions We demonstrate that a room temperature stable peptide vaccine based on known immunogenic HLA Class I bound CTL epitopes from the nucleocapsid protein can provide protection against SARS-CoV-2 infection in non-human primates.

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Competing Interest Statement

RR, TBl, SB, SC, RC, TH, LW, PL and CVH are employees of Flow Pharma. PH and TBe are Flow Pharma stockholders. The remaining authors declare no conflict of interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted April 26, 2021.
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A synthetic peptide CTL vaccine targeting nucleocapsid confers protection from SARS-CoV-2 challenge in rhesus macaques
Paul E. Harris, Trevor Brasel, Christopher Massey, C. V. Herst, Scott Burkholz, Peter Lloyd, Tikoes Blankenberg, Thomas M. Bey, Richard Carback, Thomas Hodge, Serban Ciotlos, Lu Wang, Jason E. Comer, Reid Rubsamen
bioRxiv 2021.04.24.441228; doi: https://doi.org/10.1101/2021.04.24.441228
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A synthetic peptide CTL vaccine targeting nucleocapsid confers protection from SARS-CoV-2 challenge in rhesus macaques
Paul E. Harris, Trevor Brasel, Christopher Massey, C. V. Herst, Scott Burkholz, Peter Lloyd, Tikoes Blankenberg, Thomas M. Bey, Richard Carback, Thomas Hodge, Serban Ciotlos, Lu Wang, Jason E. Comer, Reid Rubsamen
bioRxiv 2021.04.24.441228; doi: https://doi.org/10.1101/2021.04.24.441228

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