PT - JOURNAL ARTICLE AU - Claudio Counoupas AU - Alberto O. Stella AU - Nayan D. Bhattacharyya AU - Alice Grey AU - Karishma Patel AU - Angela L. Ferguson AU - Owen Hutchings AU - Carl G. Feng AU - Palendira AU - Megan Steain AU - Anupriya Aggarwal AU - Jason K. K. Low AU - Joel P. Mackay AU - Anthony D. Kelleher AU - Warwick J. Britton AU - Stuart G Turville AU - James A. Triccas TI - A single dose, BCG-adjuvanted SARS-CoV-2 vaccine induces Th1-polarized immunity and high-titre neutralizing antibodies in mice AID - 10.1101/2020.12.10.419044 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.12.10.419044 4099 - http://biorxiv.org/content/early/2020/12/10/2020.12.10.419044.short 4100 - http://biorxiv.org/content/early/2020/12/10/2020.12.10.419044.full AB - Next-generation vaccines that are safe, effective and with equitable access globally are required to prevent SARS-CoV-2 transmission at a population level. One strategy that has gained significant interest is to ‘repurpose’ existing licensed vaccines for use against COVID-19. In this report, we have exploited the immunostimulatory properties of bacille Calmette-Guérin (BCG), the vaccine for tuberculosis, to develop a SARS-CoV-2-specific and highly immunogenic vaccine candidate. 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. Boosting of BCG:CoVac-primed mice with a heterologous vaccine combination (spike protein plus alum) could further increase SARS-CoV-2 spike protein-specific antibody response. 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.Importance Effective distribution of vaccine to low- and middle-income countries is critical for the control of the COVID-19 pandemic. To achieve this, vaccines must offer effective protective immunity yet should be cheap to manufacture and meet cold chain management requirements. This study describes a unique COVID-19 vaccine candidate, termed BCG:CoVac, that when delivered as a single dose induces potent SARS-CoV-2 specific immunity in mice, particularly through generation of high-titre, anti-viral neutralising antibodies. BCG:CoVac is built on safe and well-characterised vaccine components: 1) the BCG vaccine, used for control of tuberculosis since 1921 which also has remarkable ‘off target’ effects, protecting children and the elderly against diverse respiratory viral infections; 2) Alhydrogel adjuvant (Alum), a low cost, globally accessible vaccine adjuvant with an excellent safety record in humans (part of >20 licensed human vaccines and in use >70 years); 3) Stabilized, trimeric SARS-CoV-2 spike protein, which stimulates immune specificity for COVID-19. Further assessment in humans will determine if BCG:CoVac can impart protective immunity against not only SARS-CoV-2, but also other respiratory infections where BCG has known efficacy.Competing Interest StatementThe authors have declared no competing interest.