A single dose, BCG-adjuvanted COVID-19 vaccine provides sterilising immunity against SARS-CoV-2 infection

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-...

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Autores principales:	Claudio Counoupas, Matt D. Johansen, Alberto O. Stella, Duc H. Nguyen, Angela L. Ferguson, Anupriya Aggarwal, Nayan D. Bhattacharyya, Alice Grey, Owen Hutchings, Karishma Patel, Rezwan Siddiquee, Erica L. Stewart, Carl G. Feng, Nicole G. Hansbro, Umaimainthan Palendira, Megan C. Steain, Bernadette M. Saunders, Jason K. K. Low, Joel P. Mackay, Anthony D. Kelleher, Warwick J. Britton, Stuart G. Turville, Philip M. Hansbro, James A. Triccas
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/54cf1269f483428f921decb5fa5ac562
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spelling	oai:doaj.org-article:54cf1269f483428f921decb5fa5ac5622021-12-05T12:05:34ZA single dose, BCG-adjuvanted COVID-19 vaccine provides sterilising immunity against SARS-CoV-2 infection10.1038/s41541-021-00406-42059-0105https://doaj.org/article/54cf1269f483428f921decb5fa5ac5622021-11-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00406-4https://doaj.org/toc/2059-0105Abstract 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.Claudio CounoupasMatt D. JohansenAlberto O. StellaDuc H. NguyenAngela L. FergusonAnupriya AggarwalNayan D. BhattacharyyaAlice GreyOwen HutchingsKarishma PatelRezwan SiddiqueeErica L. StewartCarl G. FengNicole G. HansbroUmaimainthan PalendiraMegan C. SteainBernadette M. SaundersJason K. K. LowJoel P. MackayAnthony D. KelleherWarwick J. BrittonStuart G. TurvillePhilip M. HansbroJames A. TriccasNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Claudio Counoupas Matt D. Johansen Alberto O. Stella Duc H. Nguyen Angela L. Ferguson Anupriya Aggarwal Nayan D. Bhattacharyya Alice Grey Owen Hutchings Karishma Patel Rezwan Siddiquee Erica L. Stewart Carl G. Feng Nicole G. Hansbro Umaimainthan Palendira Megan C. Steain Bernadette M. Saunders Jason K. K. Low Joel P. Mackay Anthony D. Kelleher Warwick J. Britton Stuart G. Turville Philip M. Hansbro James A. Triccas A single dose, BCG-adjuvanted COVID-19 vaccine provides sterilising immunity against SARS-CoV-2 infection
description	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.
format	article
author	Claudio Counoupas Matt D. Johansen Alberto O. Stella Duc H. Nguyen Angela L. Ferguson Anupriya Aggarwal Nayan D. Bhattacharyya Alice Grey Owen Hutchings Karishma Patel Rezwan Siddiquee Erica L. Stewart Carl G. Feng Nicole G. Hansbro Umaimainthan Palendira Megan C. Steain Bernadette M. Saunders Jason K. K. Low Joel P. Mackay Anthony D. Kelleher Warwick J. Britton Stuart G. Turville Philip M. Hansbro James A. Triccas
author_facet	Claudio Counoupas Matt D. Johansen Alberto O. Stella Duc H. Nguyen Angela L. Ferguson Anupriya Aggarwal Nayan D. Bhattacharyya Alice Grey Owen Hutchings Karishma Patel Rezwan Siddiquee Erica L. Stewart Carl G. Feng Nicole G. Hansbro Umaimainthan Palendira Megan C. Steain Bernadette M. Saunders Jason K. K. Low Joel P. Mackay Anthony D. Kelleher Warwick J. Britton Stuart G. Turville Philip M. Hansbro James A. Triccas
author_sort	Claudio Counoupas
title	A single dose, BCG-adjuvanted COVID-19 vaccine provides sterilising immunity against SARS-CoV-2 infection
title_short	A single dose, BCG-adjuvanted COVID-19 vaccine provides sterilising immunity against SARS-CoV-2 infection
title_full	A single dose, BCG-adjuvanted COVID-19 vaccine provides sterilising immunity against SARS-CoV-2 infection
title_fullStr	A single dose, BCG-adjuvanted COVID-19 vaccine provides sterilising immunity against SARS-CoV-2 infection
title_full_unstemmed	A single dose, BCG-adjuvanted COVID-19 vaccine provides sterilising immunity against SARS-CoV-2 infection
title_sort	single dose, bcg-adjuvanted covid-19 vaccine provides sterilising immunity against sars-cov-2 infection
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/54cf1269f483428f921decb5fa5ac562
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A single dose, BCG-adjuvanted COVID-19 vaccine provides sterilising immunity against SARS-CoV-2 infection

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