A single dose, BCG-adjuvanted COVID-19 vaccine provides sterilising immunity against SARS-CoV-2 infection. Counoupas, C., Johansen, M., Stella, A., Nguyen, D., Ferguson, A., Aggarwal, A., Bhattacharyya, N., Grey, A., Hutchings, O., Patel, K., Siddiquee, R., Stewart, E., Feng, C., Hansbro, N., Palendira, U., Steain, M., Saunders, B., Low, J., Mackay, J., Kelleher, A., Britton, W., Turville, S., Hansbro, P., & Triccas, J. npj Vaccines, Nature Research, 2021. cited By 20
A single dose, BCG-adjuvanted COVID-19 vaccine provides sterilising immunity against SARS-CoV-2 infection [link]Paper  doi  abstract   bibtex   1 download  
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 stabilised, 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 neutralising 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 neutralised 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. © 2021, The Author(s).
@ARTICLE{Counoupas2021,
author={Counoupas, C. and Johansen, M.D. and Stella, A.O. and Nguyen, D.H. and Ferguson, A.L. and Aggarwal, A. and Bhattacharyya, N.D. and Grey, A. and Hutchings, O. and Patel, K. and Siddiquee, R. and Stewart, E.L. and Feng, C.G. and Hansbro, N.G. and Palendira, U. and Steain, M.C. and Saunders, B.M. and Low, J.K.K. and Mackay, J.P. and Kelleher, A.D. and Britton, W.J. and Turville, S.G. and Hansbro, P.M. and Triccas, J.A.},
title={A single dose, BCG-adjuvanted COVID-19 vaccine provides sterilising immunity against SARS-CoV-2 infection},
journal={npj Vaccines},
year={2021},
volume={6},
number={1},
doi={10.1038/s41541-021-00406-4},
art_number={143},
note={cited By 20},
url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-85120166235&doi=10.1038%2fs41541-021-00406-4&partnerID=40&md5=2ca0ba283661efbaa183752b3a050e9f},
affiliation={School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia; Tuberculosis Research Program at the Centenary Institute, The University of Sydney, Sydney, NSW, Australia; Centre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, NSW, Australia; Kirby Institute, University of New South Wales, Sydney, NSW, Australia; Department of Clinical Immunology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; RPA Virtual Hospital, Sydney Local Health District, Sydney, NSW, Australia; School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW  2006, Australia; Sydney Institute for Infectious Diseases and Charles Perkins Centre, The University of Sydney, Camperdown, NSW, Australia},
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 stabilised, 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 neutralising 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 neutralised 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. © 2021, The Author(s).},
keywords={aluminum potassium sulfate;  bcg covac;  BCG vaccine;  coronavirus spike glycoprotein;  immunoglobulin G antibody;  neutralizing antibody;  SARS-CoV-2 antibody;  SARS-CoV-2 vaccine;  unclassified drug;  vaccine adjuvant;  virus antigen, adult;  animal cell;  animal experiment;  animal model;  animal tissue;  antibody response;  antigen specificity;  Article;  asymptomatic infection;  BCG vaccination;  controlled study;  coronavirus disease 2019;  cytokine release;  drug formulation;  experimental coronavirus disease 2019;  female;  human;  immunostimulation;  local lymph node assay;  male;  mouse;  Mycobacterium bovis BCG;  nonhuman;  nose smear;  popliteal lymph node;  single drug dose;  sterilizing immunity;  Tfh cell;  Th1 cell;  trimerization;  Vero C1008 cell line},
correspondence_address1={Triccas, J.A.; School of Medical Sciences, Australia; email: jamie.triccas@sydney.edu.au; Hansbro, P.M.; Centre for Inflammation, Australia; email: Philip.Hansbro@uts.edu.au},
publisher={Nature Research},
issn={20590105},
language={English},
abbrev_source_title={npj Vaccines},
document_type={Article},
source={Scopus},
}

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