The journal Nature recently reported that tuberculosis (TB) vaccine developers discovered TB vaccine is much more effective if it is injected directly into the veins of monkeys rather than into the skin. Researchers at the University of Pittsburgh School of Medicine and the National Institute of Allergy and Infectious Diseases (NIAID) found that administering BCG—the only vaccine available to treat tuberculosis—intravenously rather than by injection into the skin, boosted the ability of the vaccine to protect rhesus macaques from infection. The results were reported in the January 2020 issue of the journal Nature.1
Senior author JoAnne Flynn, PhD, professor of microbiology and molecular genetics at the Pitt Center for Vaccine Research said:
The effects are amazing. When we compared the lungs of animals given the vaccine intravenously versus the standard route, we saw a 100,000-fold reduction in bacterial burden. Nine out of 10 animals showed no inflammation in their lungs.
2B People Infected with TB that Kills 2M People Annually
Worldwide, 2 billion people are infected with TB, with 10 million new cases of active TB diagnosed each year and 2 million deaths.2 3 There has been a global investment of $7 billion in the health of people with TB,4 but more people die from TB than from any other infectious disease and the vast majority have been vaccinated.2
In 2017, there were 9,088 cases of TB reported in the United States, with 515 deaths. In 2018, the U.S. had the lowest number of TB cases (9,025) and lowest incidence rate (2.8 cases per 100,000) on record.5
Tuberculosis is a bacterial infection caused by a bacterium called Mycobacterium tuberculosis (Mtb) and has been known to humans since ancient times.6 7 The bacteria usually attack the lungs (pulmonary TB), but TB bacteria can attack any part of the body such as the kidney, spine, and brain (disseminated TB). Not everyone infected with Mtb becomes sick and, as a result, two TB-related conditions exist: latent TB infection and TB disease. If not treated properly, TB disease can be fatal.3 6
Century-Old Live BCG Vaccine Most Widely Used in World
Bacille Calmette-Guerin (BCG) is a live, attenuated vaccine developed in 1921 and is still the only TB vaccine used today.3 7 Given to infants via a needle under the skin, the BCG vaccine helps protect against disseminated TB, but is far less effective at preventing pulmonary TB, which is the major cause of illness and deaths in people when they reach their teens or adulthood.8 Effectiveness against pulmonary TB in older children and adults ranges from 0 percent to 80 percent.9 Although not routinely used in the U.S., BCG is the most widely used vaccine in the world and has been given to more than 4 billion individuals.3 In the U.S., the vaccine is only recommended for people who meet specific high risk criteria.10
The antibiotic streptomycin was first used in 1943 and was the first of several antibiotics used to treat tuberculosis.7 The discovery of antibiotics generated optimism in fighting TB, but drug resistance developed rapidly and multi-drug resistant TB (MDR-TB) continues to be a significant problem globally.3 People diagnosed with TB must take antibiotics for many months.11
Future IV Administration of TB Vaccine to Adolescents and Adults?
Authors of the Nature article described their finding that intravenous BCG prevents or substantially limits Mtb infection in highly susceptible rhesus macaques as having important implications for vaccine delivery and clinical development, claiming it provides “a paradigm shift towards developing vaccines focused on preventing TB infection to prevent latency, active disease, and transmission.” They say their data supports “clinical development of IV delivery of BCG for use in adolescents or adults in whom modeling predicts the greatest effect on TB transmission, and suggest that the IV route may improve the protective capacity of other vaccine platforms.”8
The team next plans to test whether lower doses of intravenous BCG could offer the same level of protection without the side effects, which they said mostly consisted of temporary inflammation in the lungs. “We’re a long way from realizing the translational potential of this work,” Flynn said. “But eventually we do hope to test in humans.”
In September, the NIAID awarded $30 million in first-year funding to establish three new research centers to accelerate progress in developing a new TB vaccine12 to replace the existing, but unreliable, BCG vaccine.10
TB and Poverty Closely Linked
Tuberculosis and poverty are closely linked. The World Health Organization (WHO) estimates that, globally, low- and lower middle-income countries account for more than 90 percent of TB cases and deaths.13
Infection with TB is not just the result of poverty, however, since the economic burden of the disease also creates poverty. In any society, rich or poor, TB tends to impact heavily on the poorest and most marginalized and vulnerable groups, such as migrant communities, people with substance use or mental health issues, people who are homeless or in live in poor quality housing, people with weakened immune systems or who are aged, and people with a history of prison. People who live in absolute poverty are more likely to experience conditions that favor the spread of Mtb: poorly ventilated or overcrowded conditions, malnutrition and disease, and limited access to health care.4
Daniel Carter, a research fellow at the London School of Hygiene and Tropical Medicine, co-authored a study published in May 2018 in Lancet Global Health15 that found that programs to tackle poverty could be just as effective in the fight against TB as medicines and vaccines.16 He said:
Science is sexy but poverty elimination is not. If a biomedical tool were to show the same efficacy on TB it would be immediately implemented, but expanding social programs requires more political will and ambition from health and development leaders.
Carter acknowledges drugs and vaccines for TB play an important role, but added:
Eradicating TB will never be about DNA sequencing or shorter drug regimens. Biomedical innovation takes money and time—two things TB patients do not have. Anti-poverty policies are available now and the evidence suggests they work. The battle to end TB is not just against a pathogen, but an ideology.
The WHO has committed to global eradication of TB by the year 2050.7
1 Darrah, PA, Zeppa, JJ, Maiello, P. et al. Prevention of tuberculosis in macaques after intravenous BCG immunization Nature January 2020; 577: 95–102.
2 Changed route of immunization dramatically improves efficacy of TB vaccine Technology.org Jan. 3, 2020.
3 Luca S, Mihaescu T. History of BCG Vaccine. Maedica (Buchar) 2013; 8(1): 53–58.
4 Tuberculosis is a disease the world could control. But will it? STAT News Sept. 26, 2018.
5 U.S. Centers for Disease Control and Prevention. Reported Tuberculosis in the United States, 2018. CDC.gov Sept. 6, 2019.
6 CDC. Basic TB Facts. CDC.gov Mar. 20, 2016 (accessed Jan. 5, 2020).
7 Dutta, Sanchari Sinha. History of Tuberculosis. News-Medical Jan. 7, 2020.
8 Tuberculosis Vaccine Efficacy Boosted Dramatically by IV Administration Genetic Engineering & Biotechnology News Jan. 3, 2020.
9 World Health Organization. Safety update of BCG vaccine. WHO.int July 14, 2017 (accessed Jan. 5, 2020).
10 CDC. TB Vaccine (BCG). CDC.gov Mar. 15, 2016 (accessed Jan. 5, 2020).
11 CDC. Treatment for TB Disease. CDC.gov Apr. 5, 2016 (accessed Jan. 5, 2020).
12 U.S. National Institutes of Health NIH awards contracts to advance tuberculosis immunology research. NIH.gov Sept. 26, 2019 (accessed Jan. 5, 2020).
13 What is the relationship between TB and poverty? StopTB.org (accessed Jan. 5, 2020).
14 TB and poverty TBAlert.org (accessed Jan. 5, 2020).
15 Carter DJ, Glaziou P, et al. The impact of social protection and poverty elimination on global tuberculosis incidence: a statistical modeling analysis of Sustainable Development Goal 1 The Lancet Global Health May 2018; 6(5): e514-e522.
16 Summers H. Eradicating poverty would dramatically reduce TB cases, study finds. The Guardian Mar. 24, 2018.