Vaccine Info

Bacille Calmette-Guerin (BCG) Vaccine

BCG Vaccine Description

Bacille Calmette-Guerin (BCG) vaccine is an attenuated, live culture preparation of the Bacillus of Calmette and Guerin (BCG) strain of Mycobacterium bovis. The TICE® strain used in this BCG vaccine preparation was developed at the University of Illinois from a strain originated at the Pasteur Institute.

BCG is a vaccine against tuberculosis, with protective non-specific effects against other respiratory tract infections and in vivo studies, and reported morbidity and mortality reductions as high as 70%. Mycobacterium tuberculosis (Mtb), the ethiological agent of tuberculosis (TB).

Many foreign-born persons have been BCG-vaccinated. As an example, India, with the world's highest TB burden, introduced BCG in mass immunization beginning in 1948.

TB is the leading cause of death from infectious disease worldwide, causing about 1.3 million deaths per year, mostly in the developing world. The respiratory virus M tuberculosis is spread via airborne transmission and more often affects men, who account for 60% of all cases, according to a recent study published by the CDC in May 2020.

Newborns and infants have the greatest benefit from BCG vaccination. Routine neonatal vaccination is recommended by the WHO in countries with moderate to severe prevalence of tuberculosis.

The reduction in childhood mortality may be due to epigenetic reprogramming of the nucleotide-binding oligomerization domain receptor. This is because of suggestions the BCG vaccine has other beneficial effects on the immune system that could protect against other infections. A 2019 observational study reported the vaccine is related to fewer deaths from certain infections other than from TB in low-income countries.

The biological interaction between Mtb and the human host is complex and only partially understood, says the WHO.

The U.S. NIH says the BCG vaccine is a fairly safe vaccine and it is not associated with severe complications.

And recently, a non-peer-reviewed study published on June 12, 2020, found that mandatory BCG was associated with a significantly slower climb in both confirmed cases and deaths during the first 30-day period of an outbreak.

Furthermore, a study published don July 31, 2020, found linear mixed models revealed a significant effect of mandated BCG policies on the growth rate of both cases and deaths after controlling for median age, gross domestic product per capita, population density, population size, net migration rate, and various cultural dimensions.

In the absence of evidence, the WHO does not recommend BCG vaccination for the prevention of COVID-19 disease. The WHO continues to recommend neonatal BCG vaccination in countries or settings with a high incidence of tuberculosis.

However, there are active phase 3 and 4 clinical trials in the USA, Australia, and the Netherlands evaluating the potential protective benefits from BCG vaccination related to COVID-19 disease prevention.

The BCG vaccine is not generally recommended for use in the USA because of the low risk of infection with Mycobacterium tuberculosis, says the CDC. In the USA, BCG should be considered for only very select people who meet specific criteria and in consultation with a TB expert.

The BCG Atlas is an open-source database of global BCG vaccination policies and practices founded in 2011.

BCG Vaccine Indication

BCG is used in many countries to prevent childhood tuberculous, meningitis, and other diseases. The BCG vaccine also helps fight other viruses, such as respiratory infections. TB is a serious infection that affects the lungs and sometimes other parts of the body, such as the bones, joints, and kidneys.

For example, one study conducted in West Africa found that children who were vaccinated with BCG had about a 50% reduction in overall mortality, largely because the vaccine reduced respiratory infections and sepsis, or blood poisoning.

A study published on May 2, 2019, reported the effect of BCG on an experimental viral infection in humans has been demonstrated. These effects are thought to be mediated via the induction of innate immune memory and heterologous lymphocyte activation, resulting in enhanced cytokine production, macrophage activity, T-cell responses, and antibody titers.

On April 6, 2020, researchers at the Johns Hopkins Bloomberg College of Public Well being discovered that the COVID-19 mortality fee amongst countries that use the Bacillus Calmette-Guérin (BCG) vaccination was eight instances lower than in these that don’t.

In the USA, BCG vaccination should be considered for very select persons who meet specific criteria and in consultation with a TB expert, says the CDC

And, BCG vaccination should not be given to persons who are immunosuppressed (e.g., persons who are HIV infected) or who are likely to become immunocompromised (e.g., persons who are candidates for organ transplant).

BCG vaccination should only be considered for children who have a negative tuberculin skin test and who are continually exposed, and cannot be separated from, adults who are untreated or ineffectively treated for TB disease or have TB caused by strains resistant to isoniazid and rifampin.

Furthermore, BCG vaccination should not be given during pregnancy. Even though no harmful effects of BCG vaccination on the fetus have been observed, further studies are needed to prove its safety.

BCG vaccination may also be recommended for older children who have an increased risk of developing TB, such as children who have recently arrived from countries with high levels of TB, including those in Africa, the Indian subcontinent, parts of southeast Asia, parts of South and Central America, and parts of the Middle East, and children who have come into close contact with somebody infected with respiratory TB, says the CDC.

A single dose of M. bovis bacillus Calmette-Guérin immunotherapy has a great therapeutic benefit in the treatment of a non-invasive form of bladder cancer. It is administered intravesically and proven benefits include the delay and prevent progression of the malignancy.

The BRACE phase 3 clinical trial, last updated on August 20, 2020, intends to recruit 10,000 healthcare workers in the UK, Australia, the Netherlands, Spain, and Brazil.

BCG Vaccine Dosage

The formulation of international requirements for the manufacture and control of the BCG vaccine was first considered by the WHO Expert Committee on Biological Standardization in its thirteenth report.

Approved dose: BCG vaccine can be given either intracutaneously or intradermally. Research is currently being conducted on respiratory administration since natural infection, and sensitization to Mycobacterium tuberculosis in humans tend to occur in the respiratory system.

BCG Vaccine News

  • October 11, 2020 - The University of Exeter is leading the UK arm of the trial, called the 'BCG vaccination to Reduce the impact of COVID-19 in healthcare workers' (BRACE) Trial. The UK joins study centers in Australia, the Netherlands, Spain, and Brazil in the largest trial of its kind.

  • October 3, 2020 - Texas A&M researchers are looking into a potential vaccine that may help with COVID-19. In addition to the medical professionals that have participated in the BCG vaccine study, more first responders such as firefighters and police officers can now see if they are eligible for the study.

  • September 24, 2020 - Fiocruz and the Murdoch Children’s Research Institute, in Australia, announced they will begin testing the BCG vaccine on 3,000 healthcare professionals, to verify the protection of the immunizer against Covid-19 as well. The trial, which was initially expected to be carried out only in the state of Mato Grosso do Sul, will be expanded to the state of Rio de Janeiro. Coordinated in Brazil by Fiocruz researchers Julio Croda and Margareth Dalcolmo, the research was approved by the National Committee of Ethics in Research.

  • September 21, 2020 - Harvard Medical School updated a phase 3 study: The purpose of this study is to assess the efficacy of Bacille Calmette-Guérin (BCG) vaccination compared to placebo in reducing severe Covid-19 disease among elderly residents of skilled nursing facilities.

  • September 21, 2020 - Usually, non-randomized studies can provide evidence only of correlations, not actual causation. But the type of analysis that the Chaisemartins applied is different. “The regression discontinuity method we used is considered almost as reliable as a randomized controlled trial in terms of teasing out correlation from causation."

  • August 23, 2020 - Study: Using information from the Swedish public health agency, researchers determined that 'While the effect of a recent vaccination must be evaluated, we provide strong evidence that receiving the BCG vaccine at birth does not have a protective effect against COVID-19 among middle-aged individuals.'

  • August 22, 2020 - The BMC is going to conduct a BCG vaccine trial among 250 seniors in India as per recommendations of the Indian Council of Medical Research.

  • August 17, 2020 - "It has been known for years that some vaccines can offer protection against diseases that they're not targeting against. Probably the best example is the BCG vaccine, which is used to try to prevent tuberculosis. It can prevent people from acquiring malaria," said Andrew Bradley, the Chair of the Mayo Clinic COVID Research Task Force. Bradley says the best theory is called immune training – that is your body, in preparing to defend itself from one disease, unintentionally protects it from another.

  • August 11, 2020 - Our findings demonstrated the potential effectiveness of the booster BCG vaccine, specifically the booster in preventing Covid-19 infections in an elevated-risk healthcare population.

  • August 5, 2020 - A new analysis suggests that mandated BCG vaccination can be effective in the fight against COVID-19.

  • July 28, 2020 - This epidemiological study assessed the global linkage between BCG vaccination and COVID-19 mortality. Signals of BCG vaccination effect on COVID-19 mortality are influenced by social, economic, and demographic differences between countries. After mitigating multiple confounding factors, several significant associations between BCG vaccination and reduced COVID-19 deaths were 'observed.' In various European countries, BCG vaccination indicated that every 10% increase in the BCG index was associated with a 10.4% reduction in COVID-19 mortality. However, these results fail to confirm the null hypothesis of no association between BCG vaccination and COVID-19 mortality and suggest that BCG could have a protective effect. 

  • July 20, 2020 - ICMR is studying the efficacy of the BCG tuberculosis vaccine against COVID-19 among the elderly. Approximately 1,500 healthy volunteers above 60 years of age will be administered one dose of 0.1ml BCG vaccine intradermally and followed up closely for a period of six months.

  • July 18, 2020 - The National Institute for Research in Tuberculosis in Chennai has initiated a multi-centric study to investigate whether the Bacille Calmette Guerin (BCG) vaccine can prevent and/or reduce the severity of COVID-19 disease among elderly individuals aged 60 years and above residing in hotspots for SARS-CoV2.

  • July 9, 2020 - Researchers at the National Institute of Allergy and Infectious Diseases of the U.S. NIH identified an 'associated' linkage between the very old Bacille Calmette-Guerin (BCG) and the reduction in COVID-19 disease, after comparing mortality rates around the world. 
  • July 3, 2020 - Researchers at the University of Sydney and Centenary Institute are repurposing an existing tuberculosis vaccine Bacille Calmette-Guérin (BCG) with major components of the SARS-CoV-2 virus, creating a new vaccine candidate called BCG:CoVac. In BCG:CoVac, the BCG vaccine is used as a vehicle to deliver distinctive proteins that originate from the SARS-CoV-2 virus surface. The goal is for the human immune system to develop a memory of SARS-CoV-2 and develop immunity.
  • June 17, 2020 - The latest survey results of Global Fund-supported programs across 106 countries show widespread disruptions to TB vaccine service delivery as a result of the COVID-19 pandemic: 78% of TB programs reported disruption to BCG vaccination services (17% with high or very high disruptions).
  • June 12, 2020 -  A non-peer-reviewed study found that mandatory BCG was associated with a significantly slower climb in both confirmed cases and deaths during the first 30-day period of an outbreak. This analysis suggests that mandated BCG vaccination can be effective in the fight against COVID-19.
  • June 11, 2020 - The Washington Post wrote 'Can old vaccines from science's medicine cabinet ward off coronavirus? ... Prominent researchers hope to test the vaccine against the coronavirus.'
  • May 28, 2020 - Bulgarian scientists suggest that the Balkan country's high rate of BCG vaccination—as well as an early lockdown—helped it to escape the worst of the pandemic. "BCG generates a powerful immune stimulation.
  • May 27, 2020 - A Phase III, two-group multicentre, randomized controlled trial in up to 10,078 healthcare workers to determine if BCG vaccination reduces the incidence and severity of COVID-19 disease.
  • May 26, 2020 - The NIH published a Bacillus Calmette Guerin (BCG) summary by Chika N. Okafor; Ayesan Rewane; Ifeanyi I. Momodu.
  • May 25, 2020 - A vaccine developed by Pune's Serum Institute of India (SII) is currently being tested at several Pune hospitals like - Ruby Hall, KEM Pune, Jehangir Hospital. Serum is carrying out phase 3 clinical trials of the Recombinant-BCG vaccine in 30 locations across the nation, as per reports.
  • May 20, 2020 - Researchers at Baylor College of Medicine and four other institutions around the country are working to find out if it also can work against COVID-19. They are now recruiting for a clinical trial to test the vaccine. “Epidemiological studies show that if you’re BCG vaccinated, you have a decreased rate of other infections,” said Dr. Andrew DiNardo, assistant professor of medicine – infectious diseases at Baylor.
  • May 19, 2020 - Can the BCG vaccine protect against COVID-19?
  • May 13, 2020 - A study published in JAMA does not support the idea that BCG vaccination in childhood has a protective effect against COVID-19 disease later in adulthood.n this cohort of Israeli adults aged 35 to 41 years, BCG vaccination in childhood was associated with a similar rate of positive test results for SARS-CoV-2 compared with no vaccination.
  • May 7, 2020 - Texas A&M University researchers vaccinated more than 50 health care workers on Wednesday as they started a clinical trial for a vaccine they believe can mitigate the effects of COVID-19. The BCG vaccinations administered at the Bryan Medical Center were the first ones in the U.S. clinical trial. BCG won’t prevent people from contracting COVID-19, but researchers believe it may allow a person’s immune response to kill nearly any type of infection, meaning it essentially broadly strengthens people’s immune response.
  • May 4, 2020 - Researchers at Baylor College of Medicine and 4 other institutions around the country are working to find out if the BCG vaccine can work against COVID-19. They are now recruiting for a clinical trial to test the vaccine.
  • April 30, 2020 - An article published in The Lancet says 'If the BCG vaccine or another inducer of trained immunity provides non-specific protection to bridge the gap before a disease-specific vaccine is developed, this would be an important tool in the response to COVID-19 and future pandemics.'
  • April 29, 2020 - This Phase 3 study evaluates the efficacy of BCG to improve the clinical course of Covid-19 infection and to prevent absenteeism in order to safeguard continuous patient care.
  • April 28, 2020 - Dr. Jeffrey Cirillo at the Texas A&M Health Science Center is leading a group of world-renown institutions in a vaccine clinical trial that could prevent COVID-19 disease cases in just 6-months. This phase 4 vaccine study will include 1,800 participants and researchers from Harvard’s School of Public Health, the University of Texas MD Anderson Cancer Center in Houston, Cedars Sinai Medical Center in Los Angeles, and the Baylor College of Medicine in Houston.
  • April 8, 2020: A non-peer-reviewed study found a significant difference in the CFR between the two groups of countries. Our data further support the view that universal BCG vaccination has a protective effect on the course of COVID-19 probably preventing progression to severe disease and death.
  • April 7, 2020:  A phase 3 study is an Open-label, two-group, randomized controlled trial in up to 4,170 healthcare workers to determine if BCG vaccination reduces the incidence and severity of COVID-19 disease during the 2020 pandemic.
  • April 6, 2020 - Researchers on the Johns Hopkins Bloomberg College of Public Well being discovered that the COVID-19 mortality fee amongst countries that use the Bacillus Calmette-Guérin (BCG) vaccination was eight instances lower than in these that don’t.
  • March 2020:  Countries with a national program of whole population BCG vaccination appear to have a lower incidence and death rate from COVID-19. This may be due to the known immunological benefits of BCG vaccination.
  • March 12, 2020:  Our results show that BCG and BCGΔBCG1419c protect T2D mice against TB via different participation of T and B lymphocytes, dendritic cells, and pro-inflammatory cytokines.
  • December 2019 - An observational study reported the vaccine is related to fewer deaths from certain infections other than from TB in low-income countries.
  • September 25, 2019:  This retrospective review was a 60-year follow-up of a clinical trial of the BCG vaccine that included 2963 participants vaccinated at a median age of 8 years.
  • May 2, 2019 - The discovery of innate immune memory has greatly improved our understanding of the mechanisms underlying the non-specific effects induced by BCG vaccination. However, a full understanding of the molecular mechanisms that underlie this phenomenon is still evolving.
  • December 29, 2018:  In T1D, BCG vaccination restored blood sugars to near normal, even in patients with advanced disease of >20 years duration. This clinically important effect may be driven by the resetting of the immune system and the shifting of glucose metabolism from overactive oxidative phosphorylation, a state of minimal sugar utilization, to aerobic glycolysis, a state of high glucose utilization, for energy production.
  • May 30, 2017:  Studies in mice have shown a beneficial effect of the BCG vaccine against allergic asthma, multiple sclerosis, and diabetes. However, the understanding of its mechanism is still fragmentary and requires further in-depth research. Some observational or intervention studies in humans have also suggested a beneficial effect, but definitive evidence for this requires confirmation in carefully conducted prospective studies.
  • September 1995 This CDC report updates and replaces previous recommendations regarding the use of Bacillus of Calmette and Guerin (BCG) vaccine for controlling tuberculosis (TB) in the United States (MMWR 1988;37:663-4, 669-75). 
  • 1995 - Generation of nitric oxide and clearance of interferon-gamma after BCG infection are impaired in mice that lack the interferon-gamma receptor.
  • 1994 - Efficacy of BCG Vaccine in the Prevention of Tuberculosis: Meta-analysis of the Published Literature.

BCG Vaccine Clinical Trials

BCG is currently involved in 102 active and recruiting clinical trials covering various conditions. Click here to review the various ongoing clinical trials. Active BCG Clinical Trials Focused on Preventing SARS-CoV-2 Infections From Developing COVID-19 Disease include the following:

  • Clinical Trial NCT04327206: BCG Vaccination to Protect Healthcare Workers Against COVID-19 (BRACE) - last update on August 20, 2020.
  • Clinical Trial NCT04328441: Reducing Health Care Workers Absenteeism in Covid-19 Pandemic Through BCG Vaccine (BCG-CORONA) - last update on April 29, 2020.
  • Clinical Trial NCT04348370: BCG Vaccine for Health Care Workers as Defense Against COVID 19 (BADAS) - last update on May 27, 2020.
Updated
10/26/2020 - 02:46