A single dose, BCG-adjuvanted COVID-19 vaccine provides sterilizing immunity against SARS-CoV-2 infection in mice
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Abstract
Global control of COVID-19 requires broadly accessible vaccines that are effective against SARS-CoV-2 variants. In this report, we exploit the immunostimulatory properties of bacille Calmette-Guérin (BCG), the existing tuberculosis vaccine, to deliver a vaccination regimen with potent SARS-CoV-2-specific protective immunity. Combination of BCG with a stabilized, trimeric form of SARS-CoV-2 spike antigen promoted rapid development of virus-specific IgG antibodies in the blood of vaccinated mice, that was further augmented by the addition of alum. This vaccine formulation, BCG:CoVac, induced high-titre SARS-CoV-2 neutralizing antibodies (NAbs) and Th1-biased cytokine release by vaccine-specific T cells, which correlated with the early emergence of T follicular helper cells in local lymph nodes and heightened levels of antigen-specific plasma B cells after vaccination. Vaccination of K18-hACE2 mice with a single dose of BCG:CoVac almost completely abrogated disease after SARS-CoV-2 challenge, with minimal inflammation and no detectable virus in the lungs of infected animals. Boosting BCG:CoVac-primed mice with a heterologous vaccine further increased SARS-CoV-2-specific antibody responses, which effectively neutralized B.1.1.7 and B.1.351 SARS-CoV-2 variants of concern. These findings demonstrate the potential for BCG-based vaccination to protect against major SARS-CoV-2 variants circulating globally.
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SciScore for 10.1101/2020.12.10.419044: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: ) Animal Ethics and Welfare Committee, which adhere to the Australian Code for the Care and Use of Animals for Scientific Purposes (2013) as set out by the National Health and Medical Research Council of Australia.
IRB: The study protocol was approved by the RPA ethics committee (Human ethics number X20-0117 and 2020/ETH00770) and by the participants’ verbal consent.
Consent: The study protocol was approved by the RPA ethics committee (Human ethics number X20-0117 and 2020/ETH00770) and by the participants’ verbal consent.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Immunization and blood collection: … SciScore for 10.1101/2020.12.10.419044: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: ) Animal Ethics and Welfare Committee, which adhere to the Australian Code for the Care and Use of Animals for Scientific Purposes (2013) as set out by the National Health and Medical Research Council of Australia.
IRB: The study protocol was approved by the RPA ethics committee (Human ethics number X20-0117 and 2020/ETH00770) and by the participants’ verbal consent.
Consent: The study protocol was approved by the RPA ethics committee (Human ethics number X20-0117 and 2020/ETH00770) and by the participants’ verbal consent.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Immunization and blood collection: Female C57BL/6 (6-8 weeks of age) were purchased from Australian BioResources ( Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Cells were surface stained with Fixable Blue Dead Cell Stain (Life Technologies) and the marker-specific fluorochrome-labelled antibodies rat anti-mouse CD4-AF700 (clone RM414, 1:200, BD cat#557956), rat anti-mouse CD8-APCy7 (clone 53-6.7, 1:200, BD cat#557654), rat anti-mouse CD44-FITC (clone IM7, 1:300, BD cat#561859). anti-mouse CD4-AF700suggested: (SouthernBiotech Cat# 1540-27, RRID:AB_2794844)anti-mouse CD8-APCy7suggested: Noneanti-mouse CD44-FITCsuggested: (SouthernBiotech Cat# 1500-02, RRID:AB_2794773)Experimental Models: Cell Lines Sentences Resources After the virus-plasma incubation, 40 μl virus/plasma mixture was added to Vero E6 cells seeded in 384-well plates at 5 × 103 cells per well in a final volume of 40 μl. Vero E6suggested: NoneExperimental Models: Organisms/Strains Sentences Resources Immunization and blood collection: Female C57BL/6 (6-8 weeks of age) were purchased from Australian BioResources ( C57BL/6suggested: NoneResults 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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
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.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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