RT Journal Article
SR Electronic
T1 A synthetic peptide CTL vaccine targeting nucleocapsid confers protection from SARS-CoV-2 challenge in rhesus macaques
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.04.24.441228
DO 10.1101/2021.04.24.441228
A1 Paul E. Harris
A1 Trevor Brasel
A1 Christopher Massey
A1 C. V. Herst
A1 Scott Burkholz
A1 Peter Lloyd
A1 Tikoes Blankenberg
A1 Thomas M. Bey
A1 Richard Carback
A1 Thomas Hodge
A1 Serban Ciotlos
A1 Lu Wang
A1 Jason E. Comer
A1 Reid Rubsamen
YR 2021
UL http://biorxiv.org/content/early/2021/04/26/2021.04.24.441228.abstract
AB 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.Competing Interest StatementRR, 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.