6684 Multi-Dose BCG Vaccination for Protection Against COVID-19 Disease and Other Respiratory Infections in Subjects with Type 1 Diabetes Late in the US Pandemic

Abstract Disclosure: W. Kühtreiber: None. E. Hostetter: None. G.E. Wolfe: None. M. Vaishnaw: None. R. Goldstein: None. E. Bulczynski: None. N. Hullavarad: None. J.E. Braley: None. H. Zheng: None. D.L. Faustman: None. A Phase II clinical trial previously reported that multiple doses of the bacillus Calmette-Guerin (BCG) vaccine, originally developed for tuberculosis prevention, could protect at-risk individuals with type 1 diabetes (T1D) against COVID-19 disease and infectious diseases early in the pandemic in the United States (US) (Cell Rep Med 2022). As SARS-CoV-2 evolved, COVID-19 disease became more transmissible, but less lethal. In a new, Phase III, randomized, double-blinded, placebo-controlled trial, we tested whether at-risk individuals with T1D given multi-dose, intradermal BCG would be protected against COVID-19 and other infectious diseases (2:1 randomization; BCG: n=93; placebo: n=48). The trial was conducted late in the COVID-19 pandemic during sequential dominance of Beta, Gamma, Delta and Omicron variants. All participants were US citizens and were negative for prior BCG vaccination and negative for tuberculosis. Two co-primary endpoints were protection from COVID-19 disease and platform protection from all infectious diseases. From April 2021 to November 2022, Tokyo-strain BCG vaccination provided significant protection against COVID-19 disease (p=0.023) and strong platform protection against all infectious diseases (p<0.0001). Over the 19-month course of the study, commercial COVID-19 vaccines were rolled out. An observational analysis of the placebo control group (i.e., no BCG vaccination) showed that COVID-19 mRNA vaccination alone provided no protection from COVID-19 disease in the enrolled population (p=0.43). BCG vaccination efficacy against COVID-19 and infectious disease in T1D was unaffected by concurrent COVID-19 vaccinations (observational analysis). These data suggest that BCG has efficacy against a range of SARS-CoV-2 variants, in contrast to current COVID-19 vaccines, which have narrow efficacy against specific viral variants. Further, it shows that individuals with T1D represent a vulnerable population for whom BCG appears to be the only effective vaccine against COVID-19 disease and confirms that, in the US, BCG vaccination protects against infectious disease as well. Presentation: 6/3/2024