A Synthetic Peptide CTL Vaccine Targeting Nucleocapsid Confers Protection from SARS-CoV-2 Challenge in Rhesus Macaques
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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.
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SciScore for 10.1101/2021.04.24.441228: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources Gene expression normalization was performed using the 16 internal reference genes included in the panel. G. Study Termination: At scheduled study termination time points (14 and 21 days post-challenge for vaccinated and control macaques, respectively), animals were humanely euthanized via intravenous administration of a pentobarbital-based euthanasia solution under deep anesthesia followed by bilateral thoracotomy. H. Statistical Analysis: Descriptive statistics were performed using Microsoft Excel. Microsoft …SciScore for 10.1101/2021.04.24.441228: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources Gene expression normalization was performed using the 16 internal reference genes included in the panel. G. Study Termination: At scheduled study termination time points (14 and 21 days post-challenge for vaccinated and control macaques, respectively), animals were humanely euthanized via intravenous administration of a pentobarbital-based euthanasia solution under deep anesthesia followed by bilateral thoracotomy. H. Statistical Analysis: Descriptive statistics were performed using Microsoft Excel. Microsoft Excelsuggested: (Microsoft Excel, RRID:SCR_016137)Qlucore Omics Explorer 3.5 (Qlucore), Metascape (Metascape.org) was used to identify the discriminating variables within the NanoString gene expression data sets from BAL sample analysis that were most significantly different between vaccinated and control subjects. Metascapesuggested: (Metascape, RRID:SCR_016620)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:We note several weaknesses in our approach to demonstrate the efficacy of this experimental vaccine: 1) SARS-CoV-2 infection in Rhesus macaques resulted in only mild disease, which appears to resolve by day 10-14 post-infection. Having noted this in previous reports on the SARS-CoV-2 /rhesus model, we tried to induce more severe forms of infection using higher doses of infectious particles than previous reports. Based on clinical signs, we found little effect of the increased dose of the virus on Rhesus SARS-CoV-2 disease severity. 2) Because of the limited amount of cells recovered from the BAL, we were where unable to perform confirmatory quantitative RT-PCR analysis of the unique gene expression patterns found in vaccinated versus control BAL. Nevertheless, we found that many of our observations have been previously reported from studies in similar models, 3) Not all the macaque chest radiographs were performed on the same day in control versus vaccinated subjects, a reflection of the logistic difficulties in working under BSL ¾ conditions. We are confident, however, we have captured the chest radiographic abnormalities induced by SAR-CoV-2 infection of macaques (i.e. conspicuous consolidations and infiltrations prevalent in the caudal lobe of the right lung), and adequately shown their absence in vaccinated viral challenged macaques, 4) we only included one cynomolgus macaque in our control group. This was primarily due to macaque availability at the time the study was co...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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