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.
【저자키워드】 Protein vaccines, Experimental models of disease, 【초록키워드】 COVID-19, SARS-CoV-2, Inflammation, Vaccine, vaccination, antibody, B.1.351, T cells, SARS-CoV-2 variant, lung, Local, virus, SARS-CoV-2 variants, protective immunity, B.1.1.7, mice, BCG, K18-hACE2 mice, disease, Blood, single dose, heterologous vaccine, Lymph node, regimen, immunostimulatory, SARS-CoV-2 spike antigen, NAbs, circulating, cytokine release, Virus-specific IgG, tuberculosis vaccine, responses, effective, Cell, trimeric, PROTECT, addition, detectable, correlated, abrogated, promoted, follicular, plasma B cell, SARS-CoV-2 neutralising antibody, 【제목키워드】 COVID-19 vaccine, Immunity, SARS-COV-2 infection, single dose, provide,