TB Vaccine Shows Protection Against COVID-19 in People With T1D

Research strands involving decades of work on a wide assortment of diseases collided—successfully—recently when news came out that an “old” vaccine against tuberculosis (TB) being tested for its potential utility in treating type 1 diabetes (T1D), was also effective in warding off COVID-19 infection. Authors reported their findings in iScience.¹

The Bacillus Calmette-Guérin (BCG) vaccine has been given for about a century in most non-Western nations to children to prevent TB. For just about as long, scientists suspected that BCG could offer wider anti-infection protection, and as the years progressed, these off-target benefits began being considered more carefully and then more formally researched.² For instance, in the 1980s, patients with bladder cancer began receiving BCG to boost their immune systems.

One research team began focusing on potential benefits to individuals with T1D. In 2012, the results of a proof-of-concept trial showing that BCG could help treat T1D were published.³

After the COVID-19 pandemic began, the same team decided to launch randomized double-blinded placebo-controlled trials to test the ability of BCG to ward off COVID-19 infection in their study participants with T1D. Results of their phase 2 trial showedalmost full protection against COVID-19 in the BCG group (92% vs placebo; P = .0036)

The phase 3 trial had 2 coprimary outcomes: to see if at-risk US adults with T1D were protected against COVID-19 and other viral, bacterial, and fungal diseases by taking multiple (5 or 6 over a 2-year period) doses of powerful Tokyo-strain BCG. The results, just published, show that those outcomes were both met, with significantly high levels of protection against COVID-19 (P = .023) and all infectious diseases (P < .0001).

What’s more, in this population, particularly vulnerable to infectious disease, it had been shown that no standard COVID-19 mRNA vaccine alone provided sufficient protection from COVID-19 (P = .43). Those vaccines also neither helped nor hindered the COVID-19 protection offered by BCG.

The time element. If BCG is so effective against COVID-19, why was it not heralded as a pandemic hero? When administered intradermally to adults who have never taken BCG before, it takes at least 2 years to achieve full protection for many off-target effects. The patients in the trials had already been taking BCG (or placebo) experimentally when the pandemic, and the COVID-19–focused research, began.

Denise Faustman, MD, PhD | Image Credit: Mass General Research Institute

Given mRNA vaccination’s lack of efficacy for those with T1D, an unmet need remains, “especially as it relates to new and emerging SARS CoV-2 variants,” the authors stated. “As the pandemic continues to evolve, it will be interesting to see if we can work with the FDA to allow access to BCG vaccine for [patients with] T1D who appear to be particularly at risk for all infectious diseases,” said senior author Denise Faustman, MD, PhD, in a statement.“The BCG vaccine offers the prospect of near-lifelong protection against every variant of COVID-19, the flu, respiratory syncytial virus, and other infectious diseases.”⁴

The authors pointed out that BCG is “heralded as the safest vaccine in continuous use globally…[and] is designated an essential medicine by the World Health Organization.” It’s a live but weakened version ofMycobacterium bovis, a bacterium related to M tuberculosis, which causes TB. The off-target effects in adults of BCG vaccination, explained the authors, are caused by changes in DNA methylation of genes of the innate and adaptive immune system and of metabolism pathways. “Signaling pathways become rewired in a time frame that correlates with the slow but durable clinical improvements.”

References

1. Kühtreiber WM, Hostetter ER, Wolfe GE, et al. Late in the US pandemic, multi-dose BCG vaccines protect against COVID-19 and infectious diseases. iScience. Published online May 22, 2024. doi:10.1016/j.isci.2024.109881

2. Keener AB. A repurposed TB vaccine shows early promise against diseases like diabetes and MS. Science News. June 2, 2021. Accessed May 29, 2024. https://www.sciencenews.org/article/bcg-tb-vaccine-diseases-diabetes-multiple-sclerosis

3. Faustman DL, Wang L, Okubo Y, et al. Proof-of-concept, randomized, controlled clinical trial of Bacillus-Calmette-Guerin for treatment of long-term type 1 diabetes. PLosOne. 2012;7(8):e41756. doi:10.1371/journal.pone.0041756

4. Brown N. Century-old vaccine protects type 1 diabetics from infectious diseases. News release. Massachusetts General Hospital. May 23, 2024. Accessed May 29, 2024. https://www.massgeneral.org/news/press-release/century-old-vaccine-protects-type-1-diabetics#:~:text=BOSTON–In%20new%20research%20investigators,disease%20and%20other%20infectious%20diseases