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-...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-11-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-021-00406-4 |
| _version_ | 1797430185565356032 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T09:23:58Z |
| format | Article |
| id | doaj.art-54cf1269f483428f921decb5fa5ac562 |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-09T09:23:58Z |
| publishDate | 2021-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-54cf1269f483428f921decb5fa5ac5622023-12-02T06:25:01ZengNature Portfolionpj Vaccines2059-01052021-11-016111010.1038/s41541-021-00406-4A single dose, BCG-adjuvanted COVID-19 vaccine provides sterilising immunity against SARS-CoV-2 infectionClaudio Counoupas0Matt D. Johansen1Alberto O. Stella2Duc H. Nguyen3Angela L. Ferguson4Anupriya Aggarwal5Nayan D. Bhattacharyya6Alice Grey7Owen Hutchings8Karishma Patel9Rezwan Siddiquee10Erica L. Stewart11Carl G. Feng12Nicole G. Hansbro13Umaimainthan Palendira14Megan C. Steain15Bernadette M. Saunders16Jason K. K. Low17Joel P. Mackay18Anthony D. Kelleher19Warwick J. Britton20Stuart G. Turville21Philip M. Hansbro22James A. Triccas23School of Medical Sciences, Faculty of Medicine and Health, The University of SydneyCentre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life SciencesKirby Institute, University of New South WalesCentre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life SciencesSchool of Medical Sciences, Faculty of Medicine and Health, The University of SydneyKirby Institute, University of New South WalesTuberculosis Research Program at the Centenary Institute, The University of SydneyDepartment of Clinical Immunology, Royal Prince Alfred HospitalRPA Virtual Hospital, Sydney Local Health DistrictSchool of Life and Environmental Sciences, The University of SydneySchool of Life and Environmental Sciences, The University of SydneySchool of Medical Sciences, Faculty of Medicine and Health, The University of SydneyTuberculosis Research Program at the Centenary Institute, The University of SydneyCentre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life SciencesSchool of Medical Sciences, Faculty of Medicine and Health, The University of SydneyTuberculosis Research Program at the Centenary Institute, The University of SydneyCentre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life SciencesSchool of Life and Environmental Sciences, The University of SydneySchool of Life and Environmental Sciences, The University of SydneyKirby Institute, University of New South WalesTuberculosis Research Program at the Centenary Institute, The University of SydneyKirby Institute, University of New South WalesCentre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life SciencesSchool of Medical Sciences, Faculty of Medicine and Health, The University of SydneyAbstract 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.https://doi.org/10.1038/s41541-021-00406-4 |
| spellingShingle | 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 npj Vaccines |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41541-021-00406-4 |
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