Abstract
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.
Highlights
As of April 2021, over 1.6% of the world population have had confirmed COVID-19 disease and the new case rate is about half a million per day
SARS-CoV-2 infection in macaques is milder relative to that observed in humans [6,8,20,21], the macaque model remains the gold standard for preclinical evaluation of COVID-19 vaccines [10,19,22,23,24,25,26,27]
We provide evidence that application of this vaccine platform in SARS-CoV-2-challenged macaques provides protection from pneumonia-like pathology observed in virally challenged but unvaccinated control non-human primate (NHP) subjects, reduces viral loads as compared to unvaccinated controls, and induces changes in the gene expression patterns in recovered bronchoalveolar lavage (BAL) cells consistent with enhanced antigen presentation capacity and markers of T cells
Summary
As of April 2021, over 1.6% of the world population have had confirmed COVID-19 disease and the new case rate is about half a million per day. While the clinical course of SARS-CoV-2 infection in macaques is milder relative to that observed in humans [6,8,20,21], the macaque model remains the gold standard for preclinical evaluation of COVID-19 vaccines [10,19,22,23,24,25,26,27]. Our overall approach focuses on promoting protective T-cell immunity using synthetic peptides delivered in biodegradable microspheres together with Toll-like receptor (TLR) 4 and 9 adjuvants and differs from current COVID-19 vaccines against spike proteins. 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. 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
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