The BCG vaccine has been used for control of tuberculosis (TB) since 1921 but also has remarkable 'off target' effects that affords protection against other pathogens, particularly respiratory infections in children and the elderly. For this reason BCG vaccination is currently being trialed as a strategy to reduce the incidence and severity of COVID-19. Modified forms of BCG are also being used as ‘new generation’ vaccines for TB.
Our research program aims to develop new vaccines for important lung pathogens, with an emphasis on TB and COVID-19. We hypothesised that BCG may interact sub-optimally with dendritic cells (DCs), the cell type pivotal in shaping the adaptive immune response to infectious agents, and thus strengthening this interaction could improve BCG protective efficacy against TB. BCG engineered to express the single-chain variable fragment recognizing the endocytic C-type lectin receptor DEC205 (BCG:DEC), expressed predominately on DCs, resulted an increased functional ability of BCG:DEC to interact with DEC205-expressing cells compared to BCG alone. In mice, BCG:DEC vaccination conferred greater protection than BCG after aerosol challenge with virulent M. tuberculosis; efficacy lasted up to 20 weeks post infection, even when BCG protection had waned. We are further assessing the suitability of BCG:DEC as a strategy to improve protection against TB in humans. In parallel studies, we are also defining the suitability of BCG as part of a vaccine strategy for COVID-19. Combination of BCG with a stabilized, trimeric form of the SARS-CoV-2 spike antigen promoted rapid development of virus-specific IgG antibodies in the sera of vaccinated mice, which could be further augmented by the addition of alum. This vaccine formulation, termed BCG:CoVac, induced a Th1-biased response both in terms of IgG antibody subclass and cytokine release by vaccine-specific CD4+ and CD8+ T cells. A single dose of BCG:CoVac was sufficient to induce high-titre SARS-CoV-2 neutralizing antibodies (NAbs) that were detectable as early as 2 weeks post-vaccination; NAb levels were greater than that seen in the sera of SARS-CoV-2-infected individuals. BCG:CoVac would be broadly applicable for all populations susceptible to SARS-CoV-2 infection and in particular could be readily incorporated into current vaccine schedules in countries where BCG is currently used. The vaccine is undergoing late stage pre-clinical testing and being prepared for clinical assessment.