Tuberculosis Vaccines

Tuberculosis Vaccines 2024

According to the World Health Organization (WHO), tuberculosis (TB) is a vaccine-preventable disease, and the better use of vaccines could save up to 1.9 billion antibiotic doses annually to treat TB infections. Versions of the Bacille Calmette-Guérin (BCG) vaccine have been used for about 100 years. Since 1921, over 4 billion BCG vaccinations have been completed worldwide. Several BCG vaccines, based on different strains, are available worldwide. The Global Coalition of TB Advocates confirmed that 16 TB vaccines are available in 2024. As of November 2024, GlobalData reported that 11 TB vaccine candidates are in late-stage development globally.  

The WHO's Director-General, Dr. Tedros Adhanom Ghebreyesus, announced plans to establish a new TB Vaccine Accelerator Council in 2023. The WHO's End TB Strategy outlines the Sustainable Development Goals to End TB by 2030. The 7th Global Forum on TB Vaccines, which will be held from October 8 to 10, 2024, is convened by the Stop TB Partnership Working Group on New TB Vaccines in collaboration with IAVI, the Tuberculosis Vaccine Initiative (TBVI), and hosted by the Ministry of Health of Brazil and the Brazilian Tuberculosis Research Network.

While BCG has demonstrated significant effectiveness, protection has not been consistent against all forms in all age groups. As of November 2024, there is no universal BCG vaccination policy. 

Tuberculosis Vaccine United States

Merck's TICE® BCG vaccine is U.S. Food and Drug (FDA)-approved (STN: 103050) and produced by Organon Teknika Corp., LLC for use in the USA. The standard BCG vaccine is considered for people who meet specific criteria, such as children with a negative TB who are continually exposed and cannot be separated from adults who are untreated or ineffectively treated for TB, says the U.S. Centers for Disease Control and Prevention (CDC). 

Tuberculosis Vaccines Global

Blessina Kumar, a member of WHO's Civil Society Taskforce on TB, confirmed 16 TB vaccines were 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. The BCG Atlas is an open-source database of global BCG vaccination policies and practices. In 2002, Neonatal BCG vaccination was practiced in 157 countries and territories. 

The Serum Institute of India (SII) recombinant BCG (rBCG) vaccine TUBERVAC-rBCG was approved in 2023 as a single-dose vaccine for the prevention of TB. As of 2024, SII is the world's largest manufacturer of BCG vaccines. "The collaboration between Serum Institute of India and Immunity Bio will undoubtedly transform how we approach cancer treatment. It will improve global access to BCG, and simultaneously - the unique therapy is the key to achieving a complete solution for bladder cancer. We are truly excited to witness the incredible impact this collaboration will have on improving patient outcomes and saving countless lives," said Mr. Adar C. Poonawalla, CEO of SII, in a press release on May 3, 2024.

BCG vaccine AJV (A.J. Vaccines) is the only licensed BCG vaccine in the UK in 2023. Beginning in September 2021, eligible babies born in the UK were offered the BCG vaccine at 28 days or soon after. 

Verity Pharmaceuticals Inc. VERITY-BCG™ Strain Russian BCG-I) in Canada.

France BCG vaccine program (Pasteur 1173P2).

Brazil strain (BCG oral Mearou RJ)

Bulgarian substrain (Sofia SL222)

Japan 172 strain (Tokyo 172-1)

BCG-Denmark 1331 (Statens Serum Institut— - BCG-Denmark vaccination had a beneficial effect on herpes. However, another study concluded that it did not reduce initial QFT Plus conversion risk in healthcare workers.

Tuberculosis Vaccine Candidates

MTBVAC is the first live attenuated BCG vaccine of Mycobacterium tuberculosis isolated from a human. Bharat Biotech International Limited, in collaboration with Biofabri, has started a series of clinical trials in 2024 to evaluate the safety, immunogenicity, and efficacy of MTBVAC in India.

The M72/AS01E (M72) subunit protein vaccine candidate combined with GSK's Adjuvant System AS01 is conducting phase 3 clinical research. 

The University of Oxford conducted a phase 1 clinical trial for an aerosol-inhaled live-attenuated Mycobacterium bovis BCG. This first-in-human aerosol BCG-controlled human infection model was reported on April 12, 2024, to be sufficiently well tolerated. Further work will evaluate the utility of this model in assessing vaccine efficacy and identifying potential correlates of protection.

WHO's Product Development for Vaccines Advisory Committee (PDVAC) has called for developing a WHO-preferred product characteristic (PPC) for new TB vaccines. As of December 2023, various BCG vaccine candidates are under development, as about 14 BCG sub-strains have evolved. The Tuberculosis Vaccines Pipeline Report provides updates on the clinical development of 17 vaccine candidates. The Bill and Melinda Gates Foundation and Wellcome pledged $550 million (Gates Medical Research Institute) to support late-stage clinical trials for a new tuberculosis vaccine. 

Access to Advanced Health Institute published results of a Phase 1 clinical trial (June 2023) in collaboration with the U.S. NIH demonstrating the safety and immune responses in a novel vaccine against TB that combines several proteins from Mtb into a fusion protein (ID93) with a proprietary immune-stimulating adjuvant (GLA-SE) in a freeze-dried formulation.

BioNTech SE announced clinical trial plans for its mRNA vaccine candidate for TB on July 26, 2021. In April 2023, BioNTech initiated a Phase 1 clinical trial of BNT164, an mRNA vaccine candidate against TB, in partnership with the Bill and Melinda Gates Foundation. A Phase Ib trial (NCT05547464) conducted in Africa evaluates three dose levels of the BNT164 investigational vaccines (BNT164a1 and BNT164b1) to select a safe and tolerable dose in a three-dose schedule. A Phase Ia trial (NCT05537038) will evaluate four dose levels of the BNT164 investigational vaccines (BNT164a1 and BNT164b1) in a three-dose schedule.

SII VPM1002 is a recombinant BCG vaccine derived from the BCG Danish subtype Prague. VPM1002 expresses listeriolysin to enable the bacilli to access the host cell cytoplasm and thus potentially enhance CD8+ T-cell activation; it also induces inflammasome activation.

IDRI's ID93 + GLA-SE TB vaccine candidate was found safe and immunogenic in healthy adults on March 6, 2023. A US NIH-funded randomized clinical trial of single-vial lyophilized ID93 + GLA-SE is ongoing. ID93+GLA-SE was developed by Christopher B. Fox, Ph.D., and scientists at the Access to Advanced Health Institute and is a recombinant subunit vaccine made from four proteins of Mycobacterium tuberculosis bacteria combined with GLA-SE, an immune-stimulating adjuvant.

BIOFABRI MTBVAC is a live attenuated vaccine against TB conducting phase 3 clinical research.

The Gamaleya Federal Research Center of Epidemiology and Microbiology's GamTBvac is in Phase 3 development.

Longhorn Vaccines and Diagnostics LLC LHNVD-301 is an unconjugated, peptide-based vaccine that combines an MTB heat shock protein epitope and a peptidoglycan (PGN) epitope. PGN is a cell wall component of bacteria that plays an essential role in infections. The combination of heat shock protein and PGN generates broad reactive antibodies. It represents a novel approach that combats AMR while targeting tuberculosis by combining multiple epitopes specific to MTB and common to gram-positive bacteria into a peptide vaccine.

The National Institutes of Health recently awarded the University of Montana a $12.3 million contract to develop a novel adjuvant for TB vaccines. The grant to the University of Montana's Center for Translational Medicine will advance a TB vaccine candidate from pretrial to clinical trials.

CanSinoBio and Etana are conducting clinical research in Indonesia for the AdHu5Ag85A vaccine.

Recombinant BCG Vaccine

Recombinant BCG (rBCG) has demonstrated potent immunogenicity with CD8+ and CD4+ stimulation and improved safety compared to standard BCG in European clinical trials. rBCG strains expressing immunomodulatory factors have been investigated for 30 years to enhance immunotherapy against bladder cancer and other diseases. Serum Institute of India (SII) confirmed in May 2024 that it would manufacture next-generation recombinant BCG (iBCG). Researchers from Brazil's Butantan Institute and collaborators stated on July 3, 2024, that they are developing a recombinant BCG that increases the protection rate to 99% and has a more extended protection period.

Universal BCG Vaccine

World leaders have committed to licensing at least one new TB vaccine. The WHO-commissioned research estimates that, over 25 years, a universal BCG vaccine that is 50% effective in preventing TB could avert up to 8.5 million deaths and reduce $6.5 billion in health costs. Harvard T.H. Chan School of Public Health researchers announced on February 17, 2023, that a recent study found that introducing an effective TB vaccine in low- and middle-income countries could lead to billions of dollars in potential health and economic benefits.

Gene-Edited BCG Vaccine Candidate

In April 2024, researchers at the University of the Witwatersrand School of Pathology published a breakthrough study in TB vaccine development by gene-editing the BCG to make it more effective. A modified BCG with depletion of enzymes associated with peptidoglycan amidation induces enhanced protection against tuberculosis in mice. In vitro and in vivo experiments in this study demonstrate the feasibility of gene regulation platforms such as CRISPRi to alter antigen presentation in BCG in a bespoke manner that tunes immunity towards more effective protection against TB disease.

Tuberculosis Vaccine Vs. Treatment Cost

The global average cost for BCG vaccination is about $5.00. According to USAID, treating a tuberculosis case in the U.S. costs about $20,000, and a drug-resistant tuberculosis case can cost over $150,000.