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

Autor: Harris PE; Department of Medicine, Columbia University, P&S 10-502, 650 West 168th Street, New York, NY 10032, USA., Brasel T; Department of Microbiology & Immunology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555, USA., Massey C; Department of Microbiology & Immunology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555, USA., Herst CV; Flow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, USA., Burkholz S; Flow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, USA., Lloyd P; Flow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, USA., Blankenberg T; Flow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, USA.; Dignity Health Mercy Medical Center, Redding, CA 96001, USA., Bey TM; Dignity Health Mercy Medical Center, Redding, CA 96001, USA., Carback R; Flow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, USA., Hodge T; Flow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, USA., Ciotlos S; Flow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, USA., Wang L; Flow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, USA., Comer JE; Department of Microbiology & Immunology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555, USA., Rubsamen RM; Flow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, USA.; The Department of Anesthesiology and Perioperative Medicine, Case Western Reserve School of Medicine, Cleveland Medical Center, University Hospitals, Cleveland, OH 44106, USA.; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA 96001, USA.
Jazyk: angličtina
Zdroj: Vaccines [Vaccines (Basel)] 2021 May 18; Vol. 9 (5). Date of Electronic Publication: 2021 May 18.
DOI: 10.3390/vaccines9050520
Abstrakt: 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 × 10 8 TCID 50 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.
Databáze: MEDLINE
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