With Increasing Drug Resistance, a Better TB Vaccine Is Even More Critical
Tuberculosis (TB) is responsible for causing over 1.6 million deaths per year. In the United States, after 20 years of annual declines, the incidence of TB has leveled at approximately 3 new cases per 100,000 people, according to a new CDC report. Epidemiologic modeling indicates that eliminating the threat of TB in the United States will require additional strategies to reduce TB in the countries of origin and expand treatment of latent TB infection among foreign-born persons. Over the past 15 years, 15 new vaccine candidates have been initiated in human trials with 2 currently in large-scale efficacy trials.
Currently, there is only one vaccine available, Mycobacterium bovis bacillus Calmette-Guérin (BCG), that partially protects against tuberculosis disease. This vaccine is not widely used in the United States, but is often administered to infants and small children in TB-prevalent countries. BCG, a live, attenuated vaccine, has shown efficacy for the prevention of more serious extrapulmonary tuberculosis in young children (eg, tuberculous meningitis, miliary tuberculosis). However, when administered to newborns, BCG was not fully effective in preventing adult pulmonary tuberculosis. A review published in the journal Vaccine indicates that one of the highest priorities in TB research is to develop vaccines that are more effective than the available BCG vaccine. Researchers believe better tuberculosis control can be achieved by:
- Vaccines that protect individuals from initial infection with Mycobacterium tuberculosis
- Prevent infected individuals from progressing to active disease
- Decrease the capacity for transmission by those with active disease
Mass vaccination of all adolescents and young adults in high burden countries (regardless of infection status), even with a vaccine that is only 50–60% effective, over a 10-year period, could prevent up to 50 million cases of incident TB during the first 35 years after introduction, researchers stated.
Multidrug-resistant (MDR) TB continues to be a public health issue globally. MDR TB is caused by an organism that is resistant to at least isoniazid and rifampin, agents indicated for the treatment of susceptible TB. Extensively drug resistant TB (XDR TB) is a rare type of MDR TB that is resistant to isoniazid and rifampin, plus any fluoroquinolone and at least 1 of 3 injectable second-line agents (ie, amikacin, kanamycin, or capreomycin). While M. tuberculosis continues to become resistant to the drugs used to combat it, the authors note that "it is highly unlikely that such resistance would result in a concomitant development of resistance against otherwise effective TB vaccines."
Many of the tuberculosis vaccine candidates are based on various vectors, adjuvants, and antigens that induce classical TH1 cytokines such as interferon-gamma or TNF-alpha from either CD4+ or CD8+ T cells. Over the next five years, other novel approaches will be pursued including aerosolized adenoviral vector vaccines and other candidates, either alone or in combination.
Study authors note that more validated animal models, better understanding of a correlate of vaccine-induced protection, new cost-effective approaches to Proof of Concept trials, and greater awareness for the size of the problem and the need for a vaccine are required in efforts develop a successful TB vaccine. Head-to-head comparison studies in animal and early human studies would be ideal and mechanisms and incentives to perform such comparisons are required, they stated.
Resuming progress toward TB elimination in the United States will require intensification of efforts both in the U.S. and globally. This includes increasing U.S. efforts to detect and treat latent TB infection, strengthening systems to interrupt TB transmission in the U.S. and globally, and accelerating reductions in TB globally.
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