A single dose, BCG-adjuvanted SARS-CoV-2 vaccine induces Th1-polarized immunity and high-titre neutralizing antibodies in mice

Counoupas, C.; Stella, A.; Bhattacharyya, N.; Grey, A.; Patel, K.; Ferguson, A.; Hutchings, O.; Feng, C.; Palendira, U.; Steain, M.; Aggarwal, A.; Low, J.; Mackay, J.; Kelleher, A.; Britton, W.; Turville, S.; Triccas, J. A.

doi:10.1101/2020.12.10.419044

bioRxiv · 10.1101/2020.12.10.419044

A single dose, BCG-adjuvanted SARS-CoV-2 vaccine induces Th1-polarized immunity and high-titre neutralizing antibodies in mice

Counoupas, C.·Stella, A.·Bhattacharyya, N.·Grey, A.·Patel, K.·Ferguson, A.·Hutchings, O.·Feng, C.·Palendira, U.·Steain, M.·Aggarwal, A.·Low, J.·Mackay, J.·Kelleher, A.·Britton, W.·Turville, S.·Triccas, J. A.

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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-Guerin (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.

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Counoupas, C., Stella, A., Bhattacharyya, N., Grey, A., Patel, K., Ferguson, A., Hutchings, O., Feng, C., Palendira, U., Steain, M., Aggarwal, A., Low, J., Mackay, J., Kelleher, A., Britton, W., Turville, S., Triccas, J. A.. 2020-12-10. A single dose, BCG-adjuvanted SARS-CoV-2 vaccine induces Th1-polarized immunity and high-titre neutralizing antibodies in mice. https://doi.org/10.1101/2020.12.10.419044

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