Vaccine Info

Bacille Calmette-Guerin (BCG) Vaccine

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Staff

Last reviewed

September 26, 2023

Fact checked by

Robert Carlson, MD + Holly Lutmer PharmD

TICE® BCG Vaccine

The Merck TICE® BCG Mycobacterium Bovis Bacille Calmette-Guerin (BCG) vaccine is an attenuated, live culture preparation of the BCG strain of Mycobacterium Bovis. Mycobacterium tuberculosis (Mtb) is the ethiological agent of tuberculosis (TB). The initial BCG vaccine was developed in 1921 by French scientists Albert Calmette and Camille Guérin. The BCG vaccine was designed to protect cattle from bovine tuberculosis and was administered to a newborn baby in Paris in 1921. BCG-induced whole blood cytokines differ 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.

BCG vaccines initially targeted against TB, tuberculosis meningitis, and nonspecific protective effects against other respiratory tract infections. On January 19, 2021, Dr. Camille Locht, research director of Inserm at the Institut Pasteur de Lille, stated, "The BCG can train the cells of the innate immune system to make them more fit and active to fight against other diseases." The U.S. National Institutes of Health (NIH) says the BCG vaccine is safe. The BCG vaccine is used in many countries (Mexico, U.K., Canada) for emerging therapeutic off-target benefits for autoimmunity, such as treating bladder cancer. As of February 2023, the biological interaction between Mtb and the human host is complex and only partially understood, says the World Health Organization (WHO). The WHO 2022 Report says BCG vaccination should continue for all infants soon after birth except for those living with HIV in high tuberculosis prevalence settings. The WHO adopted requirements for the BCG vaccine in 1965, and these were updated in 1978 to reflect the increased knowledge of vaccinations and the change to freeze-dried preparations. These were modified in 1985 to amend requirements concerning the expiry date. In its thirteenth report, the WHO Expert Committee on Biological Standardization considered the formulation of international requirements for manufacturing and controlling the BCG vaccine. On September 30, 2022, the WHO published consolidated guidelines on TB: module #3.

On August 5, 2022, new research (MIS BAIR) led by the Murdoch Children's Research Institute in Australia and published in the peer-reviewed Science Advances journal showed how BCG vaccination produces 'trained immunity responses' lasting more than 14 months after administration. On August 15, 2022, research findings published by the Cell Reports Medicine journal suggested BCG platform protection against infectious diseases and vaccine efficacy takes 1-2 years to manifest, but the protection may last decades. The Rockefeller Foundation announced on September 20, 2022, that it would commit US$15 million to the Global Fund to Fight AIDS, TB, and Malaria.

As of September 2023, the TICE® BCG vaccine is U.S. Food and Drug Administration (FDA)-approved. However, the U.S. Centers for Disease Control and Prevention (CDC) says the BCG vaccine is not generally recommended for use in the U.S. because of the minimal risk of infection with Mycobacterium tuberculosis. The BCG Atlas is an open-source database of global BCG vaccination policies and practices founded in 2011.

BCG Vaccine Versions

As of September 2023, there are various BCG vaccines and candidates under development, as about 14 sub-strains of BCG have evolved. Merck's TICE® BCG vaccine is available in the U.S. in 2023. BCG vaccines are available in countries such as the U.S., Canada, China, Cuba, Ethiopia, Jamacia, Japan, Germany, UK, Mexico, Europe, Brazil, Korea, Russia, Spain, South Africa, Quebec, India (1948), New Zealand, Australia, Venezuela, and Nigeria.

BCG Vaccine Price

The UNICEF data shows the awarded price of BCG vaccine per dose is nominal. The U.S. CDC Vaccine Price List was last updated in December 2022. Many pharmacies in the U.S. price BCG vaccines over $100.00 for one vial. The global TB Vaccine revenue is expected to increase by over 3% per year to 2027, based on various Reports. Additional BCG vaccine discount information is posted at InstantRx™.

BCG Vaccine Tuberculosis 2023

Tuberculosis (TB) is a vaccine-preventable disease, says the WHO. On January 24, 2023, PLOS Medicine published a research article: The cost and cost-effectiveness of novel tuberculosis vaccines in low- and middle-income countries: A modeling study. Our analysis projected that an effective new TB vaccine could offer significant health and economic benefits from 2028 to 2050. The Lancet published an early-release survey on August 10, 2022 - Infant BCG vaccination and risk of pulmonary and extrapulmonary TB throughout the life course: a systematic review and individual participant data meta-analysis. Interpretation: Our results suggest that BCG vaccination at birth prevents tuberculosis in young children but is also ineffective in adolescents and adults. Immunoprotection, therefore, needs to be boosted in older populations.

The U.S. CDC says 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 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. For example, the Do More by 2024 initiative in Georgia has reduced TB and drug-resistant TB incidence by 50% since 2015.

In 1994, a study was published - Efficacy of BCG Vaccine in the Prevention of Tuberculosis: Meta-analysis of the Published Literature.

BCG Alzheimer's Disease

The JAMA Network published an Original Investigation on May 19, 2023, led by investigators at Massachusetts General Hospital and Brigham and Women's Hospital, that concluded that the BCG vaccine was associated with a significantly lower rate and risk of Alzheimer's disease and related dementia in a cohort of patients with bladder cancer when accounting for death as a competing event. This phase 2 clinical trial is ongoing.

A mini-review published on June 27, 2022, points to ways immune cells can mediate between BCG vaccination and AD to support the wellness of the central nervous system. On February 22, 2022, MDPI published BCG Vaccination and Plasma Amyloid: A Prospective, Pilot Study with Implications for Alzheimer's Disease - participants tended to have higher values of Aβ42/Aβ40 ratio after BCG vaccine administration.

BCG Bladder Cancer

The study of BCG anti-tumor activity began in 1929. BCG is the most common intravesical immunotherapy for treating early-stage bladder cancer, according to Cancer.org. Non-muscle-invasive bladder cancer (NMIBC) is well-suited to benefit from BCG immunotherapy. Since 1977, BCG vaccination has been one of the most successful immunotherapies and the "standard of care for patients with bladder cancer." Unfortunately, the End Drug Shortages Alliance confirmed in February 2023 that 20% of the organizations were not providing complete BCG vaccinations to eligible cancer patients. Bladder cancer vaccine news is posted at this link.

BCG Type 1 Diabetes

Various studies are testing if BCG vaccine therapy can improve Type 1 Diabetes blood sugar control through changes in metabolism.

BCG Eczema

The Murdoch Children's Research Institute's initial study findings were published in the journal Allergy on August 24, 2021, which showed that the BCG vaccine had a modest beneficial effect in preventing eczema in high-risk infants. However, a single dose of BCG-Denmark soon after birth could reduce the incidence of eczema in infants with two atopic parents.

BCG HIV

Coinfection with Mtb and HIV is a lethal combination, says the WHO. In sub-Saharan Africa, where HIV is most prevalent, the annual incidence of TB has risen to more than 300 cases per 100,000 inhabitants. In some of these places, nearly 50% of the HIV-infected population is coinfected with TB, and more than two-thirds of TB patients are infected with HIV. The lifetime risk of developing TB is as high as 30-50% for HIV-infected persons. In some parts of southeast Asia, an estimated 20-25% of TB cases will be directly attributable to HIV, confirms the WHO.

For neonates born to mothers with an unknown HIV status and neonates with an unknown HIV status born to HIV-infected mothers (regardless of their ART status), the WHO recommends BCG vaccination, as the benefits outweigh the risks. For a neonate confirmed by virologic testing to be positive for HIV, it is recommended that BCG vaccination be delayed until ART has been started.

Experts at Fred Hutchinson Cancer Center suggested in a study published in The Lancet HIV on October 11, 2022, that future TB vaccine development clinical trials should ensure people living with HIV have access to safe and effective TB vaccines.

On June 27, 2022, The Lancet Infectious Disease published the results from a phase 2 study on HIV-infected children in South Africa. The researchers' Interpretation: The VPM1002 vaccine candidate was less reactogenic than BCG and not associated with serious safety concerns. Both vaccines were immunogenic, although responses were higher with the BCG vaccine.

In October 2020, the journal Nature published a BCG vaccine review that stated 'the (i) potential TB vaccine candidates that can be exploited for use as a dual vaccine against TB/HIV copandemic (ii) progress made in the realm of TB/HIV dual vaccine candidates in a small animal model, NHP model, and human clinical trials (iii) the failures and promising targets for a successful vaccine strategy while delineating the correlates of vaccine-induced protection.'

BCG Pregnancy

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

BCG 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.

BCG Dosage

In its thirteenth report, the WHO Expert Committee first considered forming international requirements to manufacture and control the BCG vaccine on Biological Standardization. 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); US FDA; Medline.gov; U.K. - 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. When used to protect against TB, BCG is injected into the skin. Keep the vaccination area dry for 24 hours after receiving it, and keep it clean until you cannot tell the vaccination area from the skin around it.

BCG Side Effects

Tell your healthcare provider promptly about any unusual or severe symptoms after receiving this vaccine or directly to the Vaccine Adverse Event Reporting System - www.vaers.hhs.gov.

BCG United Kingdom

In the U.K. and various countries, BCG vaccination is administered to newborn infants at risk of TB. The WHO suggests BCG programs for different age groups are equally effective against TB during puberty. BCG vaccines have effectively protected children against the more rare severe forms of TB, such as TB meningitis. The Lancet Global Health published a study in September 2022 that found BCG vaccination at birth does provide significant protection against TB disease among children under five years old.

Public Health England (PHE) announced on July 27, 2021, that eligible babies 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. On September 15, 2021, the U.K.'s PHE updated its fact sheet. The Lancet on Sept. 7, 2021, and Cancer Immunology on June 24, 2022. Epidemiologist Christine Stabell Benn and colleagues found (Mar. 2012) that BCG administered to children with low birth weight reduced all-cause mortality in these children by about 40% in the first year of life.