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 M. Rubsamen

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


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.

Original languageEnglish (US)
Article number520
Issue number5
StatePublished - May 2021


  • Animal model
  • MHC class I peptide
  • Macaque
  • SARS-CoV-2
  • T cell
  • Vaccine

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Drug Discovery
  • Infectious Diseases
  • Pharmacology (medical)


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