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.

Details

Title
A single dose, BCG-adjuvanted COVID-19 vaccine provides sterilising immunity against SARS-CoV-2 infection
Author
Counoupas Claudio 1   VIAFID ORCID Logo  ; Johansen, Matt D 2   VIAFID ORCID Logo  ; Stella, Alberto O 3 ; Nguyen, Duc H 2 ; Ferguson, Angela L 1   VIAFID ORCID Logo  ; Aggarwal Anupriya 3 ; Bhattacharyya, Nayan D 4 ; Grey, Alice 5 ; Hutchings, Owen 6 ; Patel Karishma 7 ; Siddiquee Rezwan 7 ; Stewart, Erica L 8   VIAFID ORCID Logo  ; Feng, Carl G 4   VIAFID ORCID Logo  ; Hansbro, Nicole G 2 ; Umaimainthan, Palendira 8 ; Steain, Megan C 4 ; Saunders, Bernadette M 2 ; Low Jason K K 7 ; Mackay, Joel P 7 ; Kelleher, Anthony D 3 ; Britton, Warwick J 9 ; Turville, Stuart G 3 ; Hansbro, Philip M 2   VIAFID ORCID Logo  ; Triccas, James A 10   VIAFID ORCID Logo 

 The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health, Camperdown, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X); Tuberculosis Research Program at the Centenary Institute, The University of Sydney, Sydney, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X) 
 Centre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, Australia (GRID:grid.117476.2) (ISNI:0000 0004 1936 7611) 
 Kirby Institute, University of New South Wales, Sydney, Australia (GRID:grid.1005.4) (ISNI:0000 0004 4902 0432) 
 Tuberculosis Research Program at the Centenary Institute, The University of Sydney, Sydney, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X) 
 Royal Prince Alfred Hospital, Department of Clinical Immunology, Sydney, Australia (GRID:grid.413249.9) (ISNI:0000 0004 0385 0051) 
 RPA Virtual Hospital, Sydney Local Health District, Sydney, Australia (GRID:grid.410692.8) (ISNI:0000 0001 2105 7653) 
 The University of Sydney, School of Life and Environmental Sciences, Sydney, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X) 
 The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health, Camperdown, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X) 
 Tuberculosis Research Program at the Centenary Institute, The University of Sydney, Sydney, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X); Royal Prince Alfred Hospital, Department of Clinical Immunology, Sydney, Australia (GRID:grid.413249.9) (ISNI:0000 0004 0385 0051) 
10  The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health, Camperdown, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X); The University of Sydney, Sydney Institute for Infectious Diseases and Charles Perkins Centre, Camperdown, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20590105
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2604656494
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.