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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 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.
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1 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)
2 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)
3 Kirby Institute, University of New South Wales, Sydney, Australia (GRID:grid.1005.4) (ISNI:0000 0004 4902 0432)
4 Tuberculosis Research Program at the Centenary Institute, The University of Sydney, Sydney, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X)
5 Royal Prince Alfred Hospital, Department of Clinical Immunology, Sydney, Australia (GRID:grid.413249.9) (ISNI:0000 0004 0385 0051)
6 RPA Virtual Hospital, Sydney Local Health District, Sydney, Australia (GRID:grid.410692.8) (ISNI:0000 0001 2105 7653)
7 The University of Sydney, School of Life and Environmental Sciences, Sydney, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X)
8 The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health, Camperdown, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X)
9 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)