BCG Vaccine March 2023
The 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. The BCG vaccine was 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 preventing TB, TB meningitis, and 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 with HIV living 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 the manufacture and control of the BCG vaccine. On September 30, 2022, the WHO published consolidated guidelines on TB: module #3.
And on August 5, 2022, new research (MIS BAIR) led by the Murdoch Children's Research Institute in Australia and published in the peer-review Science Advances journal showed how BCG vaccination produces 'trained immunity responses' lasting more than 14 months after the vaccine is administered. And 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, it would commit US$15 million to the Global Fund to Fight AIDS, TB, and malaria.
As of March 2023, the BCG vaccine is U.S. Food and Drug Administration (FDA)-approved and 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. 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 March 28, 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.
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 17, 2022, the WHO director Dr. Tedros Adhanom Ghebreyesus, led the 'Ending Tuberculosis: How Do We Get There' discussion and announced plans to establish a new TB Vaccine Accelerator Council that will facilitate the licensing and use of effective novel TB vaccines. The WHO published, on December 8, 2022, an investment case for new tuberculosis vaccines. The Stop TB Partnership and Treatment Action Group review published on December 6, 2022, found the annual funding for TB research reached $1 billion for the first time in 2021.
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 large potential health and economic benefits from 2028 to 2050. The Lancet published an early-release study 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 is effective at preventing 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. The Do More by 2024 initiative in Georgia has reduced the incidence of both TB and drug-resistant TB by 50% since 2015.
BCG Alzheimer's Disease
The peer-reviewed journal MDPI published Evaluation of BCG Vaccination and Plasma Amyloid: A Prospective, Pilot Study with Implications for Alzheimer's Disease (A.D.) on Feb. 12, 2022 - both the favorable direction of change after BCG as well as the utility of the APS—a valuable surrogate A.D. biomarker—may prompt a definitive large-scale multicenter investigation of BCG and A.D. risk as determined by plasma amyloid peptide ratios and APS.
BCG Bladder Cancer
BCG is the most common intravesical immunotherapy for treating early-stage bladder cancer, 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. 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.
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. But a single dose of BCG-Denmark soon after birth could reduce the incidence of eczema in infants with two atopic parents.
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 disease 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, 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 was not associated with any 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.'
The BCG vaccination should not be given during pregnancy. 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.
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); 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 the vaccine, and keep the area 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 been found effective in protecting 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 5 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.
BCG Vaccine News For 1994 - 2023
January 9, 2023 - ImmunityBio is studying N-803 plus TICE® BCG vaccine in adults with non-muscle invasive bladder cancer CIS with or without Ta/T1 papillary disease in a phase 2/3 clinical trial.
September 1, 2022 - The Lancet Global Health published a study that found that BCG vaccination at birth does provide significant protection against TB disease. And Immunoprotection needs to be boosted in older populations.
August 9, 2022 - A study led by a BU School of Public Health researcher suggests BCG vaccine protection may begin to wane as children age and, thus, adults should receive BCG vaccine boosters.
August 5, 2022 - The immune-boosting benefits of a tuberculosis vaccine can be seen in infants more than one year after vaccination, according to results from 130 children in a new study.
December 10, 2021 - The Lancet published a study by eBioMedicine: CD4+CCR6+ T cells that dominate the BCG-induced transcriptional signature. Interpretation: This detailed characterization of BCG-induced immune responses and TCR clonotypes improves our understanding of the immune response triggered by BCG and provides evidence for an important role for CCR6+ CD4 T cells.
September 22, 2021 - BMC Gene Biology published 'The influence of the gut microbiome on BCG-induced trained immunity. Together, our findings contribute to the understanding of specific and trained immune responses after BCG vaccination.'
February 17, 2021 - In The Lancet Infectious Diseases, Sarah Prentice and colleagues report that BCG's tuberculosis vaccine protects against non-tuberculous infectious diseases.
July 14, 2020 - Based on the ACTIVATE study's interim analysis, findings show a 53% decrease in the incidence of all new infections with BCG vaccination.
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 active clinical trials covering various conditions. Click here to review the various ongoing clinical trials.