A Synthetic Peptide CTL Vaccine Targeting Nucleocapsid Confers Protection from SARS-CoV-2 Challenge in Rhesus Macaques
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 su...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/9/5/520 |
| _version_ | 1797533616669982720 |
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| author | 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 M. Rubsamen |
| author_facet | 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 M. Rubsamen |
| author_sort | Paul E. Harris |
| collection | DOAJ |
| description | 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<sup>8</sup> TCID<sub>50</sub> 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. |
| first_indexed | 2024-03-10T11:17:04Z |
| format | Article |
| id | doaj.art-678fc80ad1ba43db995b78bda5058a94 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T11:17:04Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-678fc80ad1ba43db995b78bda5058a942023-11-21T20:18:21ZengMDPI AGVaccines2076-393X2021-05-019552010.3390/vaccines9050520A Synthetic Peptide CTL Vaccine Targeting Nucleocapsid Confers Protection from SARS-CoV-2 Challenge in Rhesus MacaquesPaul E. Harris0Trevor Brasel1Christopher Massey2C. V. Herst3Scott Burkholz4Peter Lloyd5Tikoes Blankenberg6Thomas M. Bey7Richard Carback8Thomas Hodge9Serban Ciotlos10Lu Wang11Jason E. Comer12Reid M. Rubsamen13Department of Medicine, Columbia University, P&S 10-502, 650 West 168th Street, New York, NY 10032, USADepartment of Microbiology & Immunology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555, USADepartment of Microbiology & Immunology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555, USAFlow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, USAFlow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, USAFlow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, USAFlow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, USADignity Health Mercy Medical Center, Redding, CA 96001, USAFlow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, USAFlow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, USAFlow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, USAFlow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, USADepartment of Microbiology & Immunology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555, USAFlow Pharma Inc., 4829 Galaxy Parkway, Suite K, Warrensville Heights, OH 44128, USABackground: 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<sup>8</sup> TCID<sub>50</sub> 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.https://www.mdpi.com/2076-393X/9/5/520SARS-CoV-2animal modelmacaquevaccineMHC class I peptideT cell |
| spellingShingle | 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 M. Rubsamen A Synthetic Peptide CTL Vaccine Targeting Nucleocapsid Confers Protection from SARS-CoV-2 Challenge in Rhesus Macaques Vaccines SARS-CoV-2 animal model macaque vaccine MHC class I peptide T cell |
| title | A Synthetic Peptide CTL Vaccine Targeting Nucleocapsid Confers Protection from SARS-CoV-2 Challenge in Rhesus Macaques |
| title_full | A Synthetic Peptide CTL Vaccine Targeting Nucleocapsid Confers Protection from SARS-CoV-2 Challenge in Rhesus Macaques |
| title_fullStr | A Synthetic Peptide CTL Vaccine Targeting Nucleocapsid Confers Protection from SARS-CoV-2 Challenge in Rhesus Macaques |
| title_full_unstemmed | A Synthetic Peptide CTL Vaccine Targeting Nucleocapsid Confers Protection from SARS-CoV-2 Challenge in Rhesus Macaques |
| title_short | A Synthetic Peptide CTL Vaccine Targeting Nucleocapsid Confers Protection from SARS-CoV-2 Challenge in Rhesus Macaques |
| title_sort | synthetic peptide ctl vaccine targeting nucleocapsid confers protection from sars cov 2 challenge in rhesus macaques |
| topic | SARS-CoV-2 animal model macaque vaccine MHC class I peptide T cell |
| url | https://www.mdpi.com/2076-393X/9/5/520 |
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