TY - JOUR T1 - A single dose, BCG-adjuvanted COVID-19 vaccine provides sterilizing immunity against SARS-CoV-2 infection in mice JF - bioRxiv DO - 10.1101/2020.12.10.419044 SP - 2020.12.10.419044 AU - Claudio Counoupas AU - Matt D. Johansen AU - Alberto O. Stella AU - Duc H. Nguyen AU - Angela L. Ferguson AU - Anupriya Aggarwal AU - Nayan D. Bhattacharyya AU - Alice Grey AU - Karishma Patel AU - Rezwan Siddiquee AU - Erica L. Stewart AU - Carl G. Feng AU - Nicole G. Hansbro AU - Umaimainthan Palendira AU - Megan C. Steain AU - Bernadette M. Saunders AU - Jason K. K. Low AU - Joel P. Mackay AU - Anthony D. Kelleher AU - Warwick J. Britton AU - Stuart G Turville AU - Philip M. Hansbro AU - James A. Triccas Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/06/03/2020.12.10.419044.abstract N2 - 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 stabilized, 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 neutralizing 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 neutralized 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.Competing Interest StatementThe authors have declared no competing interest. ER -