Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

First Author:  P Wang et al 

Journal/preprint name: bioRxiv 

Paper DOIhttps://doi.org/10.1101/2020.08.24.264192 

Tags: Vaccines, Immunology/Immunity  

Summary: 

Ca-DelMut is an attenuated SARS-CoV-2 vaccine candidate. Hamsters vaccinated with Ca-DelMut were fully protected from live challenge with two different SARS-CoV-2 strains. Immunization reduced viral titers to undetectable levels in the lungs, induced RBD specific neutralizing antibodies, abrogated weight loss and reduced lung pathology. Infection with Ca-DelMut did not induce the high levels of proinflammatory cytokines (INF-g, CCR4, IL-10, IL-21, TNF-a) seen in WT virus infections. Notably, there was no activation of IL-6, which has been recognized as a biomarker for COVID-19 disease severity. 

Research Highlights  

  1. Researchers adapted a variant of SARS-CoV-2 with a deletion in the S1/S2 junction of the spike protein, ‘Ca-DelMut 

  1. Ca-DelMut replicates efficiently in vitro 

  1. Ca-DelMut does not induce elevated levels of proinflammatory cytokines or body weight loss in a hamster model 

  1. Ca-DelMut did trigger a neutralizing antibody response in hamsters 

  1. Ca-DelMut immunized hamsters challenged with WT SARS-CoV-2 showed no body weight loss and had no signs of viral replication in the respiratory tract  

Impact for COVID-19 research:  

  • Develop a vaccine for SARS-CoV2/COVID19   

Methodologies: 

  • Study Typein vitro, in vivo (hamster) 

  • Important cell lines/viral models used:  

Cell lines: Vero E6, Calu-3 

Viral models: SARS-CoV-2 WT virus HK-13 and HK-95 for viral challenge, SARS-CoV-2 WT virus HK-001a for neutralization assay, SARS-CoV-2 Cal-DelMut as candidate vaccine 

  • Key Techniques: Anti-spike RBD IgG ELISA, intranasal vaccination of hamsters, histopathological assessment of hamster lung and nasal tissue, plaque assay, neutralization assay of sera from hamsters, qRT-PCR for cytokine profiling  

Limitations: 

  • N=3 for each sub-group, which is too small to confer statistical significance to the results. 

  • No mention of blinding e.g. for the histological analysis. 

  • No description of replicates for ELISA data. Would be good to see raw data with CVs calculated in the Supplementary Figures. 

  • Done in hamster model, rather than a non-human primate model. This may not translate well to humans. 

  • Usereplication in Vero E6 cells to claim that Ca-DelMut replicates more efficiently in vitro than WT virus, but Vero E6 is a limited model and the Calu-3 data is more equivocal. 

  • No statistical comparison included for IL-6 and IL-13 in Figure S3. 

  • Likely outside scope of study, but no long-term data on antibody titers or protective efficacy. 

  • The paper does not discuss potential safety issues with using an attenuated live virus as a vaccine, and potential to revert to a more pathogenic form in vivo.