BCG Vaccine Description
The Bacille Calmette-Guerin (BCG) vaccine is an attenuated, live culture preparation of the BCG strain of Mycobacterium Bovis. The TICE® strain used in the Merck BCG vaccine preparation was developed from a Pasteur Institute strain at the University of Illinois.
BCG is a germ related to the one that causes tuberculosis, but it doesn’t usually cause serious disease. Mycobacterium tuberculosis (Mtb) is the ethiological agent of tuberculosis (TB).
The BCG vaccine initially targeted against tuberculosis, and tuberculosis meningitis, with non-specific protective effects against other respiratory tract infections and in vivo studies, reported morbidity and mortality reductions as high as 70%. 'Some vaccines, especially those derived from live attenuated microorganisms, also have essential beneficial heterologous effects outside the target disease, wrote researchers in a study published by The Lancet on July 5, 2021.
Newborns and infants have the most significant benefit from BCG vaccination. Evidence mainly from the past two decades suggests that BCG has non-specific benefits against non-tuberculous infections in newborn babies and older adults, and offers immunotherapeutic benefits in certain malignancies such as non-muscle-invasive bladder cancer, reported The Lancet on September 7, 2021.
The WHO recommends routine neonatal vaccination in countries with moderate to severe tuberculosis prevalence. The reduction in childhood mortality may be due to epigenetic reprogramming of the nucleotide-binding oligomerization domain receptor. 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 that the vaccine is related to fewer deaths from certain infections other than TB in low-income countries.
Public Health England announced on July 27, 2021, beginning September 2021, eligible babies born on or after this date should be offered the BCG vaccine at 28 days or soon after. BCG vaccination is recommended for babies up to 1-year-old, and BCG vaccination may also be recommended for older children who have an increased risk of developing TB. And providers are required to check the record for a negative SCID result or confirm that the child was not offered SCID screening before administering the BCG vaccine.
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 relatively safe, not associated with severe complications. Many foreign-born persons in the USA have been BCG-vaccinated. For example, India introduced BCG in mass immunization with its highest TB burden in 1948.
BCG Vaccine Versions
Over 14 sub-strains of BCG have evolved and have been used as BCG vaccines in different laboratories around the world. It was suggested that the strain variation may contribute to the highly variable protective efficacy of BCG against TB observed in clinical trials.
BCG vaccine versions with marked variability in the content of live mycobacteria include but are not limited to BCG-Denmark (Statens Serum Institute); BCG- Japan, BCG-India, BCG-Bulgaria. BCG-induced whole blood cytokines differed significantly by age, vaccine formulation, and concentration. In addition, BCG-induced cytokine production correlated with CFU, suggesting that mycobacterial viability may contribute to BCG-induced immune responses. The BD commercial Middlebrook 7H11 medium was rated well.
Merck's version of the TICE® BCG organism is grown to prepare the freeze-dried cake in agar composed of the following ingredients: glycerin, asparagine, citric acid, potassium phosphate, magnesium sulfate, and iron ammonium citrate. The final preparation before freeze-drying also contains lactose. Merck's freeze-dried BCG preparation is delivered in vials, each containing 1 to 8 x 10^8 colony-forming BCG units, equivalent to approximately 50 mg of wet weight. Determination of in-vitro potency is achieved through colony counts derived from a serial dilution assay. Intradermal guinea pig testing is also used as an indirect measure of potency. Merck confirmed BCG vaccine production increases in January 2021.
Drugbanks Accession Number is DB12768; UNII: 8VJE55B0VG, 5H5854UBMZ; ATC code: J07AN01; KEGG: D03063, D06466
BCG Vaccine History
Mycobacterium Bovis bacille Calmette-Guérin (BCG), a vaccine designed to protect cattle from bovine tuberculosis, was administered for the first time to a newborn baby in Paris in 1921, reported The Lancet.
The WHO recommends neonatal BCG vaccination in countries or settings with a high incidence of tuberculosis. Recently, a non-peer-reviewed study published on June 12, 2020, found that mandatory BCG vaccination was associated with a significantly slower climb in both confirmed cases and deaths during the first 30-day period of an outbreak.
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.
Furthermore, a study published on 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.
The BCG Atlas is an open-source database of global BCG vaccination policies and practices founded in 2011.
BCG Vaccine Indication
The BCG vaccine is used in many countries to prevent childhood tuberculous, meningitis, bladder cancer, 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 other parts of the body, such as the bones, joints, and kidneys.
For example, one study conducted in West Africa found that vaccinated children with BCG had about a 50% reduction in overall mortality, largely because it reduced respiratory infections, sepsis, or blood poisoning.
A study published on May 2, 2019, reported the effect of BCG on an experimental viral infection in humans had 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.
BCG Vaccine and Tuberculosis
Tuberculosis is a vaccine-preventable disease, reported the Lancet on September 7, 2021. 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. There were an estimated 2.5 million TB cases in the African Region in 2019, accounting for 25% of the global burden. More than 500,000 African lives are lost to TB every year, reported by the World Health Organization (WHO).
In the USA, BCG vaccination should be considered for select persons who meet specific criteria and consult with a TB expert, says the CDC. Also, BCG vaccination should not be given to immunosuppressed persons (e.g., HIV infected) or persons likely to become immunocompromised (e.g., candidates for organ transplant).
BCG vaccination should only be considered for children who have a negative tuberculin skin test and are continually exposed. It cannot be separated from untreated or ineffectively treated adults for TB disease or have TB caused by strains resistant to isoniazid and rifampin.
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.
“Tuberculosis in children and adolescents has been overlooked for many years, reflected in large gaps in access to TB prevention and care. Therefore it is encouraging to see that options for the diagnosis, treatment, prevention and care for children and adolescents with TB or at risk of TB, are expanding, thanks to the generation of new evidence” said Dr. Tereza Kasaeva, Director of WHO’s Global Tuberculosis Programme, on August 26, 2021.
Beginning September 2021, eligible babies born in the UK should be offered the BCG vaccine at 28 days or soon after. However, it is 70-80% effective against the most severe forms of TB, such as TB meningitis. However, it is less effective in preventing the formation of TB that affects the lungs.
On September 6, 2021, The Lancet reported three tests are used in the USA to identify latent tuberculosis infection: the tuberculin skin test (TST) and two IFN-γ release assays (T-SPOT.TB and QuantiFERON).
BCG Vaccine and Cancer
Bacillus Calmette-Guerin is the most common intravesical immunotherapy for treating early-stage bladder cancer. It's used to help keep cancer from growing and help keep it from coming back, says Cancer.org. BCG has been one of the most successful immunotherapies and has been the "standard of care for patients with bladder cancer" since 1977.
BCG is put right into the bladder through a catheter. It reaches the cancer cells and "turns on" the immune system. The immune system cells are attracted to the bladder and attack the bladder cancer cells. So BCG must come in contact with the cancer cells to work.
A single dose of M. Bovis bacillus Calmette-Guérin immunotherapy has a great therapeutic benefit in treating a non-invasive form of bladder cancer. It is administered intravesically, and proven benefits include the malignancy's delay and prevention of progression.
On March 13, 2019, Merck stated it 'recognizes the impact the current availability of TICE BCG (BCG LIVE FOR INTRAVESICAL USE) is having on patients and their caregivers and today provided an update on the company’s long-term commitment to maintain increased production of and access to TICE BCG, a medicine for the treatment of certain forms of bladder cancer.'
On January 8, 2020, Merck announced that the U.S. Food and Drug Administration had approved KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle-invasive bladder cancer with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.
Verity Pharmaceuticals Inc. announced on September 9, 2021, that it had received approval to begin distributing VERITY-BCG™ (Bacillus Calmette-Guérin [BCG]: Strain Russian BCG-I). This approval means that hospitals and clinics across Canada will no longer see shortages of this critical drug.
BCG Vaccine and COVID-19
The WHO stated in April 2020, 'There is no evidence that the Bacille Calmette-Guérin vaccine protects people against infection with COVID-19 virus.'
On April 6, 2020, researchers at the Johns Hopkins Bloomberg College of Public Well discovered that the COVID-19 mortality fee amongst countries that use the Bacillus Calmette-Guérin vaccination was eight instances lower than those that don’t. However, active late-stage clinical trials in the USA, Australia, and the Netherlands evaluate the potential protective benefits from BCG vaccination related to COVID-19 disease prevention.
On August 5, 2020, a study published by Science Advances: Mandated Bacillus Calmette-Guérin (BCG) vaccination predicts flattened curves for the spread of COVID-19. Conclusion - Our analysis suggests that mandated BCG vaccination can be effective in the fight against COVID-19.
The BRACE phase 3 clinical trial, last updated on October 22, 2020, intends to recruit about 10,000 healthcare workers in the UK, Australia, the Netherlands, Spain, and Brazil. The BRACE trial is now the world's largest study on the off-target effects of the BCG vaccine. Since the trial launched in March 2020, more than 6,800 healthcare workers have enrolled across 36 sites in Australia, Brazil, the Netherlands, Spain, and the UK. Last updated in June 2021.
On November 20, 2020, a study by Cedars-Sinai in Los Angeles, California, raised the possibility that the BCG vaccine may help prevent coronavirus infections or reduce the disease's severity. In the new study, published in The Journal of Clinical Investigation, investigators tested the blood of more than 6,000 healthcare workers in the Cedars-Sinai Health System for evidence of antibodies to SARS-CoV-2, the virus that causes COVID-19, and also asked them about their medical and vaccination histories. They found that workers who had received BCG vaccinations in the past—nearly 30% of those studied—were significantly less likely to test positive for SARS-CoV-2 antibodies in their blood or to report having had infections with coronavirus or coronavirus-associated symptoms over the prior six months.
On March 8, 2021, The Frontiers journal published 'BCG Vaccine for COVID-19: First Verdict and Future Directions.' Since the BCG vaccine has proven protection against viral respiratory infections, several laboratories are exploring the possibility that the BCG vaccine could be used alone or synergistically to reduce COVID-19 disease severity. We conclude that in addition to protection from COVID-19 disease, SARS-CoV-2 viral production, and death, BCG clinical trials that evaluate (i) alternative routes of administration, (ii) its potential use as an adjuvant, and (iii) its potential to prevent concurrent respiratory diseases will be very informative.
A non-peer-reviewed study published on August 31, 2021, Intravenous administration of BCG protects mice against lethal SARS-CoV-2 challenge, concluded by saying, 'We propose that this protection stems from BCG-induced alterations in the composition and function of the pulmonary cellular compartment that impact the innate response to the virus and the ensuing immunopathology.'
Texas A&M University is conducting a late-stage, phase 4 clinical trial of the BCG vaccine. No study results have been published as of September 8, 2021.
BCG Vaccine and Diabetes
On June 25, 2021, researchers from Massachusetts General Hospital located in Boston, MA, presented positive updates on their trials of the bacillus Calmette-Guérin (BCG) vaccine to safely and significantly lower blood sugars. Key findings include a new understanding of how the response to BCG vaccination differs depending on a patient's age of onset and additional support for the role of BCG vaccination to alter glucose transport and change Tregs. Currently, 143 type 1 diabetics have received at least two doses of BCG, including 25 patients enrolled in a recently launched trial of adults who had pediatric onset. Pending U.S. FDA approval, MGH aims to launch a multi-center pediatric trial later in 2021.
On February 27, 2020, the Journal of Internal Medicine published a study that concluded 'New findings of immune and metabolic defects in type 1 diabetes that can be corrected with repeat BCG vaccination suggest that this therapeutic strategy may be applicable in other diseases with inadequate aerobic glycolysis, including Parkinson’s disease, dementia, depression and other disorders affecting the nervous system.'
On June 21, 2018, the journal Nature published 'Long-term reduction in hyperglycemia in advanced type 1 diabetes: the value of induced aerobic glycolysis with BCG vaccinations.' This report is on a randomized 8-year long prospective examination of type 1 diabetic subjects with the long-term disease who received two doses of the BCG vaccine. After year 3, BCG lowered hemoglobin A1c to near-normal levels for the next 5 years. These findings set the stage for further testing a known safe vaccine therapy for improved blood sugar control through changes in metabolism and durability with epigenetic changes even in advanced Type 1 diabetes.
BCG Vaccine and Eczema
A study published in the journal Allergy showed that the BCG vaccine had a modest beneficial effect in preventing eczema in high-risk infants. The benefit was greater in infants with two atopic parents, meaning those who have hay fever, asthma, or eczema. In these infants, a single dose of BCG soon after birth reduced the incidence of eczema by 25%. However, the authors noted insufficient evidence to recommend neonatal BCG vaccination for all infants to prevent eczema in the first year of life.
BCG Vaccine and Pregnancy
The 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 Vaccine and Yellow Fever
The study demonstrated the effects of BCG vaccination on genome-wide histone modifications induced in trained monocytes, which are associated with reduced levels of yellow fever virus viremia due to increased IL-1β production and release. These cross-protection effects of BCG against YFV infection confirm the non-specific effects of the BCG vaccine.
BCG Vaccine Dosage
The WHO Expert Committee first considered forming international requirements to manufacture and control the BCG vaccine on Biological Standardization in its thirteenth report. Approved dose: BCG vaccine can be given either cutaneously or intradermally. Research is currently being conducted on respiratory administration since humans' natural infection and sensitization to Mycobacterium tuberculosis occur in the respiratory system.
The timing and dose of BCG vaccination assessed by vaccination tuberculin sensitivity (1995); U.S. FDA; Medline.gov; UK - 2020; WHO.
The intact vials of BCG VACCINE should be stored refrigerated at 2–8°C (36–46°F). This agent contains live bacteria and should be protected from direct exposure.
BCG Vaccine News
September 9, 2021 - Canada approved the distribution of VERITY-BCG™ (Bacillus Calmette-Guérin [BCG]: Strain Russian BCG-I). This approval means that hospitals and clinics across Canada will no longer see shortages of this critical drug. VERITY-BCG™ is an adjuvant therapy after transurethral resection (TUR) of a primary or relapsing superficial papillary urothelial cell carcinoma of the bladder stage Ta (grade 2 or 3) or T1 (grade 1, 2, or 3), without concomitant carcinoma in situ. It is only recommended for stage Ta grade 1 papillary tumors when there is a high risk (>50%) of tumor recurrence.
August 29, 2021 - India media reported, 'BCG works well in some geographic locations and not so well in others.'
August 26, 2021 - The WHO Global Tuberculosis Programme announced important updates to guidance on managing tuberculosis (TB) in children and adolescents. This includes new recommendations on diagnostic options, treatment regimens, treatment decision algorithms, and optimal models of care for the delivery of child and adolescent TB services.
August 24, 2021 - The Murdoch Children's Research Institute reported initial study findings published in the journal Allergy, which showed that the BCG vaccine had a modest beneficial effect in preventing eczema in high-risk infants. At this stage, however, the authors noted there is insufficient evidence to recommend neonatal BCG vaccination for all infants to prevent eczema in the first year of life.
August 19, 2021 - The Irish Times published 'Vaccine needed for tuberculosis pandemic.' “Infants are very susceptible to getting TB,” says Prof Hazel Dockrell, an Irish-born immunologist at the London School of Hygiene & Tropical Medicine. “BCG is still widely given to babies to protect from disseminated forms of TB, but it gives variable protection to adolescents and adults [against lung disease].” She describes TB as “a much trickier infection to protect against than SARS-CoV-2”.
August 5, 2021 - The Weather Channel published an article that stated: A team of researchers from the CMR-National Institute for Research in Tuberculosis and the ICMR-National Institute of Epidemiology, both based in India, has found that the BCG vaccine used to reduce the threat of tuberculosis may provide older people with some protection against COVID-19. Analysis of the samples revealed a significant decrease in several cytokines (small proteins that control immune system cell activity) among these vaccinated individuals like IL-6, type 1 interferons, interleukin-2 (IL-2), and TNF-alpha GM-CSF.
August 4, 2021 - A new study published by Science Advances stated, 'Our results demonstrated that BCG vaccination resulted in diminished plasma levels of types 1, 2, and 17 and other proinflammatory cytokines and type 1 interferon. BCG vaccination also decreased plasma levels of CC, CXC chemokines, APPs, MMPs, and growth factors. Furthermore, plasma levels of the aforementioned parameters were significantly lower in vaccinated individuals when compared to unvaccinated control individuals. Thus, our study demonstrates the immunomodulatory properties of BCG vaccination and suggests its potential utility in nonspecific vaccination of COVID-19 by down-modulating pathogenic inflammatory responses.' The scientists from the ICMR-National Institute for Research in Tuberculosis and the ICMR-National Institute of Epidemiology said that 'the BCG vaccine dampens inflammation by lowering the levels of inflammation-related marker proteins. It also checks the secretion of specific proteins discharged during lung inflammation.'
August 4, 2021 - Science Advances published a new RESEARCH ARTICLE: Effect of BCG vaccination on proinflammatory responses in elderly individuals. These researchers stated 'Our results demonstrated that BCG vaccination resulted in diminished plasma levels of types 1, 2, and 17 and other proinflammatory cytokines and type 1 interferon. In addition, BCG vaccination also resulted in decreased plasma levels of CC, CXC chemokines, APPs, MMPs, and growth factors. Furthermore, plasma levels of the aforementioned parameters were significantly lower in vaccinated individuals when compared to unvaccinated control individuals. Thus, our study demonstrates the immunomodulatory properties of BCG vaccination and suggests its potential utility in nonspecific vaccination of COVID-19 by down-modulating pathogenic inflammatory responses.'
August 3, 2021 - The Canadian Medical Journal published 'Bacillus Calmette–Guérin scar flare after an mRNA SARS-CoV-2 vaccine.' Sporadic cases of BCG scar inflammation were recently reported after second doses of the mRNA-1273 (Moderna) and BNT162b2 mRNA vaccines. This phenomenon is likely to be under-reported. However, BCG scar flares after vaccination with current mRNA vaccines against SARS-CoV-2 appear to be benign, as in the cases presented here, and should not alarm physicians, limit vaccinations, nor be a reason for vaccine hesitancy.
July 31, 2021 - Linking India's entire Universal Immunisation Programme (UIP) under the ministry of health and family welfare to CoWin is in the works. UIP includes vaccines like BCG, DPT, OPV, Measles, among others, reported the Time of India.
July 27, 2021 - Scientists from the Hackensack Meridian Center for Discovery and Innovation (CDI) in NJ were awarded $6.4 million from the National Institutes of Health (NIH) to pursue new tuberculosis (TB) vaccine concept. The team proposes to improve Bacille Calmette-Guérin (BCG) by engineering it to stimulate the development and communication of B cells, an important part of the immune system. With this strategy, the researchers hope to develop a second-generation TB vaccine that provides reliable protection from new infections and can even help to cure existing TB infections by complementing antibiotic therapy.
July 21, 2021 - Bavesh Kana, with The Conversation, wrote a new article: TB prevention has relied on the same vaccine for 100 years. It's time for innovation.
July 16, 2021 - The WHO announced it is joining partners, civil society, and affected people & communities worldwide in calling for increased and sustained investments in TB vaccine development. A new vaccine that is effective across all age groups, particularly adults and adolescents, will be critical to reaching End TB targets. Vaccines also offer the best chance to contain the spread of multi-drug-resistant TB.
July 14, 2021 - Spanish biopharmaceutical company Biofabri and IAVI, an international nonprofit research organization focused on developing vaccines and antibodies against infectious and neglected diseases, announced their intention to partner on efficacy trials of tuberculosis vaccine candidate MTBVAC. MTBVAC can be used as an alternative to BCG vaccination in infants and prevent TB disease in adolescents and adults.
July 13, 2021 - Nascent Biotech, Inc. and its collaboration partner, Manhattan BioSolutions, announced promising preliminary preclinical results for the COVID-19 vaccine candidate now progressing under joint development by the Partners. The vaccine candidate currently in development is based on genetically engineered BCG bacteria, which the addition of SARS-CoV-2 protein fragments has modified. In addition, next-generation vaccine candidates, each representing a different combination of a receptor-binding domain fragment of a spike protein and a conserved nucleocapsid antigen, have been successfully constructed and validated to express viral protein fragments in the BCG bacteria.
July 5, 2021 - The Lancet published: Assessing the effect of BCG revaccination on long-term mortality. Increasing evidence accumulated since the mass vaccination programs of the 20th century suggests that some vaccines, especially those derived from live attenuated microorganisms, also have important beneficial heterologous effects outside the target disease. Probably the vaccine that has been most studied concerning its protective heterologous effects is BCG.
July 5, 2021 - The Lancet published: The effect of BCG revaccination on all-cause mortality beyond infancy: 30-year follow-up of a population-based, double-blind, randomized placebo-controlled trial in Malawi. We found little evidence of any beneficial effect of BCG revaccination on all-cause mortality. The high proportion of deaths attributable to non-infectious causes beyond infancy, and the long time interval since BCG for most deaths, might obscure any benefits.
July 1, 2021 - The TB action plan for England, 2021 to 2026 will improve TB prevention, detection, and control, enabling the UK to meet its commitment to the World Health Organization End TB Strategy and eliminate TB in England 2035. This plan will include increasing latent tuberculosis infection testing (where groups at risk of TB are screened to see if they carry the bacteria without displaying symptoms) and offering the BCG vaccine to all those eligible within 4 weeks of birth.
July 1, 2021 - The Scientist published an article written by Anthony King: Although BCG is currently the only available TB vaccine, researchers have been developing a better option for decades.
June 17, 2021 - The World Health Organization (WHO) today released updated global lists of high burden countries for tuberculosis (TB), HIV-associated TB, and multidrug/rifampicin-resistant TB (MDR/RR-TB). The new WHO lists are for 2021–2025 and replace those previously used between 2016 and 2020.
June 9, 2021 - An Australian-led study investigates whether it’s possible to predict who remains susceptible to SARS-CoV-2 variants after having COVID-19 or receiving a COVID-19-specific vaccine. The BRACE trial is now the world’s largest study on the off-target effects of the BCG vaccine. Since the trial launched in March 2020, more than 6,800 healthcare workers have enrolled across 36 sites in Australia, Brazil, the Netherlands, Spain, and the UK.
June 2, 2021 - Science News reported: “Everybody kept getting signals, often from human data, saying this microorganism is doing beneficial things … whether it was allergy or autoimmunity or multiple sclerosis or diabetes,” says immunologist Denise Faustman of Harvard Medical School. “Over the last 10 years, that dataset has just grown and grown.” Dr. Faustman is in the midst of a 150-person safety and efficacy trial of BCG in adults with type 1 diabetes. In a small study published in 2018, her team previously showed that the vaccine could safely improve blood glucose control in patients with the long-term disease who continued taking insulin.
May 7, 2021 - The World Health Organization convenes a Guideline Development Group to advise on updates to its recommendations on managing tuberculosis in children and adolescents.
April 13, 2021 - LintonPharm Co., Ltd., a China-based biopharmaceutical company, announced that the National Medical Products Administration had authorized the company to proceed with a Phase 1/2 clinical trial evaluating the safety and efficacy of catumaxomab in patients with Non-Muscle-Invasive Bladder Cancer whose tumors have recurred due to BCG vaccine failure.
April 12, 2021 - The American Journal of Preventive Medicine published a new study: Childhood Bacillus Calmette–Guérin Vaccination and Its Association With Less Severe COVID-19 Pneumonia. Conclusions: BCG vaccination received in childhood is associated with less severe COVID-19 pneumonia (p=0.028) and milder liver function deficiency, in addition to a lower death rate in BCG-vaccinated patients versus non-vaccinated individuals. Overall, the death rate was significantly lower in the BCG-vaccinated group (4.2%, 5/118) than in the unvaccinated group (19.0%, 55/290. Another unexpected finding is less liver dysfunction in COVID-19 patients with BCG immunization history, which is likely associated with metabolic reprogramming that alters certain metabolites that can function as cofactors in some liver enzymes. However, definitive proof of the BCG vaccine's benefit must validate this broad approach, which remains lacking.
April 7, 2021 - The WHO stated, 'Those in the highest economic quintile are five times more likely to deliver their babies in health facilities and have their babies vaccinated with BCG than those in the lowest quintile.'
March 24, 2021 - GAVI reported, 'Despite the universal vaccination of neonates and infants in TB-endemic countries, Mycobacterium tuberculosis still kills more people worldwide than any other infectious pathogen – approximately 1.4 million deaths each year. Approximately a quarter of the world’s population is infected with it, of whom 5-10% will develop TB disease during their lifetimes. '
March 23, 2021 - Study: BCG Vaccine-Induced Trained Immunity and COVID-19: Protective or Bystander? This review focuses on BCG-related cross-protection and acquisition of trained immunity, as well as the correlation between BCG vaccination and COVID-19 incidence and mortality.
March 22, 2021 - The ECDC published Tuberculosis surveillance and monitoring in Europe 2021 –2019 data. This report provides an overview of the latest TB epidemiological situation. It is published jointly by the WHO Regional Office for Europe and the European Centre for Disease Prevention and Control.
March 9, 2021 - At the Ukraine Ministry of Health's request, the United Nations Children’s Fund (UNICEF) delivered 450,000 BCG vaccines to protect children from tuberculosis. UNICEF procured these vaccines. This BCG vaccine is manufactured by the Serum Institute of India and is pre-qualified by the WHO. Later, Ukraine will receive another 640,000 doses. According to the Public health Centre of Ukraine, 88.8% of children under one year of age were vaccinated against tuberculosis in 2020.
February 23, 2021 - The Lancet article: Quantifying the global number of tuberculosis survivors: a modeling study. The number of tuberculosis survivors alive in 2020 is more than ten times the estimated annual tuberculosis incidence. Therefore, interventions to alleviate respiratory morbidity, screen for and prevent recurrent tuberculosis, and reduce stigma should be immediately prioritized for recently treated tuberculosis survivors.
February 17, 2021 - The Lancet published a new 'BCG-induced non-specific effects on heterologous infectious disease in Ugandan neonates: an investigator-blind randomized controlled trial.' This study investigated whether BCG altered all-cause infectious disease morbidity in healthy infants in a different high-mortality setting (west Africa) and explored whether the changes are mediated via trained innate immunity. Study Interpretation: BCG vaccination protects against non-tuberculous infectious diseases during the neonatal period, in addition to having tuberculosis-specific effects. Prioritizing BCG on the first day of life in high-mortality settings might significantly benefit public health by reducing all-cause infectious morbidity and mortality.
February 17, 2021 - In The Lancet Infectious Diseases, Sarah Prentice and colleagues report that BCG's tuberculosis vaccine protects against non-tuberculous infectious diseases. Trials on infants with low birthweight in West Africa suggest that BCG vaccination reduces all-cause mortality in the neonatal period, probably because of heterologous protection against non-tuberculous infections. This study investigated whether BCG altered all-cause infectious disease morbidity in healthy infants in a different high-mortality setting and explored whether the changes are mediated via trained innate immunity.
February 11, 2021 - The University of Szeged's research team found 802 common protein fragments between the BCG vaccine and the SARS-CoV-2 virus that causes COVID-19 infection, which may play a role in the immune response against the virus. The results of a paper published in the prestigious journal Clinical and Translational Immunology may be important in elucidating the immunological link between BCG vaccination and COVID-19 disease.
February 5, 2021 - Healthcare workers are at the frontline of the coronavirus disease (COVID-19) pandemic. They will be randomized to receive a single dose of BCG vaccine or 0.9% NaCl placebo. Participants will be followed up for 12 months with a notification from a Smartphone application or phone calls (up to daily when ill) and surveys to identify and detail COVID-19 infection. Additional information on the severe disease will be obtained from hospital medical records and/or government databases. Blood samples will be collected before randomization at 3, 6, 9, and 12 months to determine exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Where required, swab/blood samples will be taken at illness episodes to assess SARS-CoV-2 infection.
Jan. 27, 2021 - Merck announced that the Board of Directors had approved plans to construct a new manufacturing facility to significantly expand production capacity for TICE® BCG (BCG Live For Intravesical Use), a medicine for the treatment of certain forms of bladder cancer. Since Merck unexpectedly became the only manufacturer of BCG for patients in many countries worldwide in 2012, increasing global demand has outpaced our current maximum manufacturing capabilities. Once this new facility is fully operational, we will triple its current manufacturing capacity, which is expected to support the anticipated demand for TICE BCG for the foreseeable future. The new facility will be part of the Maurice R. Hilleman Center for Vaccine Manufacturing in Durham, North Carolina.
January 21, 2021 - IVIA reported TB vaccine candidate being investigated to prevent TB infection in infants in Phase III priMe study.
January 19, 2021 - According to Dr. Camille Locht, research director of Inserm at the Institut Pasteur de Lille, the BCG vaccine's mechanism is the innate immune system. “The BCG can train the cells of the innate immune system to make them more fit and active to fight against other diseases. This is why we think that training the immune system with BCG will have a protective effect against organisms that have nothing to do with tuberculosis or BCG,” Dr. Locht told RFI.
December 31, 2020 - India has dispatched 2,400 vials of BCG vaccine to Male to bridge a shortfall in the Maldives' National Immunization Programme. The Ministry of Health and Ministry of External Affairs of the Government of India procured the vaccine and coordinated its dispatch with the High Commission of Maldives in Delhi, the Honorary Consul of Maldives Mumbai, the Maldivian Ministry of Foreign Affairs.
December 21, 2020 — ImmunityBio, Inc. announced positive data from the first cohort of a pivotal Phase 2/3 trial (QUILT 3.032) for non-muscle invasive bladder cancer in high-risk carcinoma in situ (CIS) disease. The data showed 51 out of 71 evaluable patients (72%) had a complete response (at any time) to intravesical BCG plus N-803 (Anktiva), with a 59% probability of these patients maintaining a complete response for at least 12 months, with a median duration of complete response of 19.2 months to date. With the observed efficacy and only 1% of patients reporting treatment-emergent serious adverse events, but none of which were treatment-related, the data support the potential for Anktiva plus BCG as a novel option for BCG unresponsive CIS, a therapeutically challenging disease. Patients with BCG unresponsive CIS disease face surgical removal of the bladder, a procedure fraught with high morbidity and mortality.
December 11, 2020 - BCG has long been known for its non-specific beneficial effects, most likely explained by epigenetic and metabolic reprogramming of innate immune cells, termed trained immunity. In this issue of the JCI, Rivas et al. add to these arguments by showing that BCG-vaccinated healthcare providers from a Los Angeles healthcare organization had less COVID-19 diagnosis and serology than unvaccinated individuals. Prospective clinical trials are thus warranted to explore BCG effects in COVID-19. We posit that beyond COVID-19, vaccines that elicit trained immunity, such as the BCG, may mitigate the impact of emerging pathogens in future pandemics. Almost one-third of the volunteers participating in the study had received earlier BCG vaccination, accompanied by a marked decrease (by approximately 30-40%) of self-reported COVID-19 diagnoses, self-reported positive COVID19 RT-PCR tests, and anti-SARS-CoV-2 specific serology. BCG vaccinations were associated with lower COVID-19 incidence, although the vaccinated group was slightly older and had more co-morbidities.
December 11, 2020 - The UN Tuberculosis High-Level Meeting Political Declaration, signed in October 2018 by more than 100 government and 360 civil society representatives, committed to treating 3·5 million children with tuberculosis by 2022. To this end, more children must be diagnosed. Unfortunately, although an estimated 12% of all tuberculosis disease is in children younger than 15 years, in 2019, only 8% of notifications involved children, a proportion that is even lower in some high-burden countries, and 16% of tuberculosis deaths occurred in this age group. Altogether, these numbers suggest substantial barriers to diagnosis and timely treatment of childhood tuberculosis and under-reporting because of difficulties in the case definition.
December 9, 2020 - Based on the capacity of BCG to (1) reduce the incidence of respiratory tract infections in children and adults; (2) exert antiviral effects in experimental models; and (3) reduce viremia in an experimental human model of viral infection, we hypothesize that BCG vaccination may induce (partial) protection against the susceptibility to and/or severity of SARS-CoV-2 infection. This phase III randomized controlled trial provides the highest validity to answer this research question. Furthermore, given the SARS-CoV-2 epidemic's immediate threat, the trial has been designed as a pragmatic study with a highly feasible primary endpoint, which can be continuously measured. This allows for the most rapid identification of a beneficial outcome that would allow other at-risk individuals, including the control population, to benefit from the intervention if and as soon as it has demonstrated efficacy and safety.
December 9, 2020 - Study: These data show BCG vaccination is safe and can protect the elderly against infections. Randomized controlled trials are underway in the Netherlands and Australia to assess whether the BCG vaccine reduces the incidence and severity of COVID‐19 in healthcare workers. Still, the ACTIVATE trial gives some hope that BCG could protect the elderly against COVID‐19.
December 4, 2020 - Study: Unlike many adjuvants, BCG decreases the incidence of lymphoid malignancies, and its effect on various autoimmunopathies is different, not necessarily harmful. The peculiar BCG vaccination effect may be related to its early impact on immature immune systems and host-BCG interactions' symbiotic character. Geo-epidemiological data on the relationship between the historical practice of using BCG vaccination in different countries and the current incidence of new coronavirus infection and mortality are presented. Historically, the medical and social reasons for the different national policies of health authorities regarding using the BCG vaccine are considered.'
November 20, 2020 - A widely used tuberculosis vaccine is associated with a reduced likelihood of contracting COVID-19 (coronavirus). The findings raise the possibility that a vaccine already approved by the U.S. Food and Drug Administration may help prevent coronavirus infections or reduce the disease's severity. The vaccine, known as Bacillus Calmette-Guérin (BCG), was developed between1908 and 1921 and is administered to more than 100 million children worldwide every year. It is FDA-approved as a drug to treat bladder cancer and as a vaccine for people at high risk of contracting TB. The BCG vaccine is currently being tested in multiple clinical trials worldwide for effectiveness against COVID-19.
November 19, 2020 - The Journal of Clinical Investigation published a Cedars-Sinai Health System study for evidence of antibodies to SARS-CoV-2 and found that workers who had received BCG vaccinations in the past—nearly 30% of those studied—were significantly less likely to test positive for SARS-CoV-2 antibodies in their blood or to report having had infections with coronavirus or coronavirus-associated symptoms over the prior 6-months than those who had not received the BCG vaccine. "It appears that BCG-vaccinated individuals either may have been less sick and therefore produced fewer anti-SARS-CoV-2 antibodies, or they may have mounted a more efficient cellular immune response against the virus," said Arditi, professor of Pediatrics and Biomedical Sciences. "We were interested in studying the BCG vaccine because it has long been known to have a general protective effect against a range of bacterial and viral diseases other than TB, including neonatal sepsis and respiratory infections."
November 17, 2020 - A new study published by The Lancet found 'Patients with high-risk non–muscle-invasive tumors that do not respond to adjuvant therapy with the standard-of-care immunotherapy, Bacille Calmette-Guérin (BCG), constitute a challenging patient population to manage and many alternative therapies are being studied. While intravesical BCG has remained the mainstay of therapy for intermediate and high-risk non–muscle-invasive bladder cancer, the therapeutic options for the muscle-invasive and advanced disease have expanded to include immunotherapy with checkpoint inhibition, targeted therapies, and antibody-drug conjugates.'
November 5, 2020 - Researchers of a trial by Parel's Haffkine Research Institute and BJ Medical College, Pune, conducted on 60 Covid patients hospitalized with breathlessness and pneumonia claimed to have found a reduction in oxygen requirement from the third or fourth day and improved x-rays and CT scan from day 7-15. No deaths in the arm got the BCG shot, while two deaths in a group got a standard line of care.
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, South Africa, and Brazil in the largest trial. “BCG has been shown to boost immunity in a generalized way, which may offer some protection against COVID-19,” stated Professor John Campbell of the University of Exeter Medical School.
October 3, 2020 - Texas A&M researchers are looking into a potential vaccine that may help COVID-19. In addition to the medical professionals who 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 - The BCG vaccine may be a potential, safe, affordable, and readily available candidate intervention to decrease the high burden of disease associated with HSV infection and recurrences, but properly controlled randomized trials are required. BCG administration led to a 1.9 to 5.5‐fold increase in survival rate following the HSV challenge (vaginal, corneal, or intraperitoneal inoculation).
September 24, 2020 - Fiocruz and the Murdoch Children’s Research Institute in Australia announced they would begin testing the BCG vaccine on 3,000 healthcare professionals to verify the immunizer's protection against Covid-19. The trial, which was initially expected to be carried out only in Mato Grosso do Sul, will be expanded to Rio de Janeiro. Coordinated in Brazil by Fiocruz researchers Julio Croda and Margareth Dalcolmo, the National Committee approved 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 only provide 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 31, 2021 - A study published by Cell: Activate: Randomized Clinical Trial of BCG Vaccination against Infection in the Elderly. Data show that BCG vaccination is safe and can protect the elderly against infections.
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 will conduct a BCG vaccine trial among 250 seniors in India as per the Indian Council of Medical Research recommendations.
August 19, 2020 - In this issue of the JCI, Koeken and de Bree et al. report that BCG reduces circulating inflammatory markers in males but not in females, while de Bree and Mouritis et al. describe how diurnal rhythms affect the degree of BCG-induced innate memory. These studies further delineate factors that influence the magnitude of responses to BCG and may be crucial to harnessing its potential benefits.
August 17, 2020 - "It has been known for years that some vaccines can offer protection against diseases that they're not targeting. The best example is the BCG vaccine used to prevent tuberculosis. In addition, it can prevent people from acquiring malaria," said Andrew Bradley, the Mayo Clinic COVID Research Task Force Chair. 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 booster BCG vaccine's potential effectiveness, 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 effectively 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's effect on COVID-19 mortality are influenced by countries' social, economic, and demographic differences. 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 studies the BCG tuberculosis vaccine's efficacy 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 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 14, 2020 - Based on the ACTIVATE study's interim analysis, findings showing a 53% decrease in the incidence of all new infections with BCG vaccination.
July 9, 2020 - Researchers at the National Institute of Allergy and Infectious Diseases of the U.S. NIH identified an 'associated' linkage between the ancient 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 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 due to the COVID-19 pandemic: 78% of TB programs reported disruption 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 effectively 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. As per reports, the serum is carrying out phase 3 clinical trials of the Recombinant-BCG vaccine in 30 locations across the nation.
May 22, 2020 - Science Direct published: BCG Vaccinations Upregulate Myc, a Central Switch for Improved Glucose Metabolism in Diabetes. This is the first documentation of BCG induction of Myc and its association with systemic blood sugar control in a chronic disease like diabetes.
May 20, 2020 - Researchers at Baylor College of Medicine and four other institutions worldwide are working to determine if it can also 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. In 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 in the U.S. clinical trial. Unfortunately, BCG won’t prevent people from contracting COVID-19. Still, 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 worldwide are working to determine 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 response to COVID-19 and future pandemics.'
April 29, 2020 - This Phase 3 study evaluates BCG's efficacy to improve the clinical course of Covid-19 infection and prevent absenteeism from safeguarding continuous patient care.
April 28, 2020 - Dr. Jeffrey Cirillo at the Texas A&M Health Science Center leads a group of world-renowned institutions in a vaccine clinical trial to prevent COVID-19 disease cases in just six 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 Medicine in Houston.
April 8, 2020: A non-peer-reviewed study found a significant difference in the CFR between the two 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, the 2020 pandemic.
April 6, 2020 - Researchers on the Johns Hopkins Bloomberg College of Public Well 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 that the vaccine is related to fewer deaths from certain infections other than 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. Numerous epidemiological, clinical, and immunological studies demonstrate that BCG vaccination impacts subsequent infections' immune response, reducing morbidity and mortality. Important lines of evidence indicating that BCG protects against viral pathogens come from experimental studies in mice showing that BCG offers protection against various DNA and RNA viruses, including herpes and influenza viruses. Recently, BCG's effect 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.
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 immune system's resetting and shifting glucose metabolism from overactive oxidative phosphorylation, a state of minimal sugar utilization, aerobic glycolysis, and 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, understanding 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 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 - The generation of nitric oxide and interferon-gamma clearance after BCG infection is impaired in mice lacking 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.