Journal
NPJ VACCINES
Volume 6, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41541-021-00406-4
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Funding
- MRFF COVID-19 Vaccine Candidate Research Grant [2007221]
- University of Sydney
- National Health and Medical Research Council (NHMRC) of Australia [1175134]
- UTS
- NHMRC Centre of Research Excellence in Tuberculosis Control [1153493]
- Rainbow Foundation
- National Health and Medical Research Council of Australia [1153493] Funding Source: NHMRC
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This study demonstrates the potential of a BCG-based vaccine to provide protection against major SARS-CoV-2 variants by inducing potent virus-specific immune responses. Pre-treatment with BCG:CoVac followed by a heterologous vaccine boosts SARS-CoV-2-specific antibody responses effectively neutralizing key variants.
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 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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