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Article

A Synthetic Peptide CTL Vaccine Targeting Nucleocapsid Confers Protection from SARS-CoV-2 Challenge in Rhesus Macaques

1
Department of Medicine, Columbia University, P&S 10-502, 650 West 168th Street, New York, NY 10032, USA
2
Department of Microbiology & Immunology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555, USA
3
Flow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, USA
4
Dignity Health Mercy Medical Center, Redding, CA 96001, USA
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The Department of Anesthesiology and Perioperative Medicine, Case Western Reserve School of Medicine, Cleveland Medical Center, University Hospitals, Cleveland, OH 44106, USA
6
Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA 96001, USA
*
Authors to whom correspondence should be addressed.
Equal contributions.
Academic Editor: Natalie Prow
Vaccines 2021, 9(5), 520; https://doi.org/10.3390/vaccines9050520
Received: 24 April 2021 / Revised: 10 May 2021 / Accepted: 13 May 2021 / Published: 18 May 2021
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
Background: Persistent transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has given rise to a COVID-19 pandemic. Several vaccines, conceived in 2020, that evoke protective spike antibody responses 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 × 108 TCID50 units of SARS-CoV-2, followed by assessment of clinical symptoms and viral load, chest radiographs, and 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 nonhuman primates. View Full-Text
Keywords: SARS-CoV-2; animal model; macaque; vaccine; MHC class I peptide; T cell SARS-CoV-2; animal model; macaque; vaccine; MHC class I peptide; T cell
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MDPI and ACS Style

Harris, P.E.; Brasel, T.; Massey, C.; Herst, C.V.; Burkholz, S.; Lloyd, P.; Blankenberg, T.; Bey, T.M.; Carback, R.; Hodge, T.; Ciotlos, S.; Wang, L.; Comer, J.E.; Rubsamen, R.M. A Synthetic Peptide CTL Vaccine Targeting Nucleocapsid Confers Protection from SARS-CoV-2 Challenge in Rhesus Macaques. Vaccines 2021, 9, 520. https://doi.org/10.3390/vaccines9050520

AMA Style

Harris PE, Brasel T, Massey C, Herst CV, Burkholz S, Lloyd P, Blankenberg T, Bey TM, Carback R, Hodge T, Ciotlos S, Wang L, Comer JE, Rubsamen RM. A Synthetic Peptide CTL Vaccine Targeting Nucleocapsid Confers Protection from SARS-CoV-2 Challenge in Rhesus Macaques. Vaccines. 2021; 9(5):520. https://doi.org/10.3390/vaccines9050520

Chicago/Turabian Style

Harris, Paul E., 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, and Reid M. Rubsamen. 2021. "A Synthetic Peptide CTL Vaccine Targeting Nucleocapsid Confers Protection from SARS-CoV-2 Challenge in Rhesus Macaques" Vaccines 9, no. 5: 520. https://doi.org/10.3390/vaccines9050520

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