New Study Reveals Insight for Tuberculosis Vaccine Development
등록일 2019년 01월 07일 월요일
수정일 2017년 11월 27일 월요일

Photo by: John Keith via Wikimedia Commons

A team of researchers from has found the possible key to create a vaccine for tuberculosis.In a partnership with Public Health England, the researchers discovered a way to trigger an immune response from unconventional T cells.

Traditional T cells are reactive with peptide complexes and major histocompatibility complex proteins.Meanwhile, unconventional T cells are reactive with lipids, small-molecule metabolites, and specially modified peptides.Unconventional T cells include CD1-restricted T cells, MR1-restricted mucosal-associated invariant T cells, MHC class Ib-reactive T cells, and γδ T cells.Unconventional T cells are currently under research to determine their therapeutic use.

In the study by the universities of Southampton and Bangor, researchers identified the specific lipids called mycolic acids, fatty substances found in Mycobacterium tuberculosis, which can be used to make unconventional T cells reactive.

"This is an exciting discovery with potential therapeutic implications for TB patients.We have shown that synthetic lipids related to those in the cell wall of Mtb are selectively targeted by T-cells.Our findings could help drive advances in vaccine development through the intelligent design of the lipid components of future TB vaccines," Dr.Salah Mansour from the Southampton University and lead author of the study.

Mycolic acids are long fatty acids prominent in the cell walls of the Mycobacterium genus.This group of bacteria includes pathogens, M.tuberculosis that causes tuberculosis and M.leprae that causes leprosy.In M.tuberculosis, mycolic acids have three main types, alpha-mycolic, methoxy-mycolic, and keto-mycolic.About 70 percent of the bacterium's mycolic acids are made up of alpha-mycolic.The other two types share the remaining 30 percent, with individual composition ranging from 10 to 15 percent.

The unique properties of mycolic acids in the tuberculosis bacteria are the reason why the disease is difficult to treat.These properties include resistance to chemical damage, dehydration, a limitation in the effects of antibiotics and germicides like carbapenems and fluoroquinolones, and the ability to hide from the immune system by growing inside macrophages.

The study findings could be proved useful for the development of future methods of prevention and treatment of tuberculosis.

How Tuberculosis Drugs Work

Tuberculosis is a major global health crisis with at least 10.4 million cases worldwide reported in 2016.An estimated 1.7 million of deaths is associated with the disease.It is also the leading infection that kills people infected with HIV, according to the Centers for Disease Control and Prevention.

The drugs used to treat infections caused by Mycobacteria are called antimycobacterials.Isoniazid is included in the first-line of broad-spectrum drugs used to treat tuberculosis.Isoniazid works by preventing the synthesis of mycolic acids of the bacteria.However, resistance can develop quickly if used alone.Other antimycobacterials included in the first broad-spectrum drugs are as follows:

- Rifampin is designed to inhibit the bacterial RNA polymerase, preventing it to form necessary proteins.

- Ethambutol works by disrupting the bacterial cell wall to increase permeability, allowing substances to pass through it.

- Pyrazinamide converts an enzyme to disrupt the cell membrane and disables the energy production of the bacteria.

- Streptomycin is an antibiotic that stops the growth of bacteria.

In case the strain of the tuberculosis bacteria is resistant to the first-line broad-spectrum drugs, a set of alternative drugs may be used to treat the disease.Amikacin blocks the bacteria's ability to produce proteins, while ciprofloxacin prevents reproduction and repair of the bacteria's DNA.Ethionamide works by disrupting the mycolic acids of the bacteria.Para-aminosalicylic acid stops the bacterial's capacity to make folic acid.

Drug resistance is also a major problem in eradicating the disease.At least five percent of infected people are resistant to both isoniazid and rifampin.About 10 percent of those have an extensively drug-resistant TB strain that resists isoniazid, rifampin, fluoroquinolones, and at least one of the alternative drugs, such as amikacin.

About seven countries have been accounted for the 64 percent of total cases of TB the world.These are India, Indonesia, China, Philippines, Pakistan, Nigeria, and South Africa.An estimated 1 million children were infected with TB and 250,000 of them died from the disease in 2016.The disease claimed the lives of the 40 percent HIV-infected patients in 2016, according to WHO.

Drugs Used for Leprosy

Leprosy was eliminated as a public health problem, defined with a prevalence rate of less than one person per 10,000 people, since 2000.The global registered cases of leprosy are 216, 108 of which come from 145 countries of the World Health Organization regions as of October 2017.The disease has a slow incubation period with symptoms manifesting between one year and 20 years.

Leprosy deformities in hands / Photo by: Bruno Jehle (B.jehle) via Wikimedia Commons

Leprosy is also caused by a mycobacterium and it is not advisable to treat the infection with a single drug.According to WHO, leprosy should be treated using a multidrug therapy model.Dapsone and rifampin are used to treat paucibacillary leprosy, patients with negative skin smear result.But multibacillary leprosy, patients with positive skin smear result, must be treated with dapsone, rifampin, and clofazimine.Clinicians cannot interchange the two sets of multidrug therapy among patients.If uncertain, it is recommended to use the MDT on multibacillary leprosy.

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