Coating Gold Nanoparticles With Bacteria: How IISc Bengaluru Researchers Plan To Fight TB

Adding another feather to its cap, the Bengaluru-based Indian Institute of Science (IISc) has designed a new way to deliver a vaccine candidate for tuberculosis, one of the biggest silent killers in India. Despite being one of the biggest preventable diseases that affect millions of lives every years, TB rarely receives the attention it deserves. 

A group of researchers from IISc, however, have designed a way to deliver a TB vaccine candidate using spherical vesicles secreted by bacteria coated on gold nanoparticles which can then be delivered to immune cells. 

The discovery can mark a significant change in the treatment cure and prevention of the deadly disease which killed 1.5 million globally in 2020, as per an estimate by the World Health Organisation. 

What is TB?

Tuberculosis is a deadly and contagious caused by the bacterium Mycobacterium tuberculosis. It kills over a million people worldwide every year.  The bacterial disease mainly affects the lungs and can spread to other parts of the body including the brain. While prolonged and persistent coughing with blood spotting is one of the most identifiable symptoms of TB, most affected by the TB bacteria do not exhibit any symptoms at all, making the disease all the harder to track and identify. Treatment isn't always required for those without symptoms. However, newer variants of the TB variant and lack of awareness have made treatment and prevention difficult. 

Are there any TB vaccines as of now?

The only effective vaccine currently in use is the BCG vaccine. It contains a weakened form of the disease-causing bacterium. When injected into our bloodstream, it triggers the production of antibodies that can help fight the disease.

While the BCG vaccine works well in children, researchers at the IISc have claimed that it is not as effective at protecting adolescents and adults. Earlier in April, the Indian Council of Medical Research (ICMR) had also confirmed that there was no prevention vaccine for TB available for household contacts expect for HIV patients or for children below six years. 

Currently, the BCG vaccine is used among children at the time of birth. The trial is being sponsored by the Indian Council of Medical Research (ICMR).

How does IISc's proposed vaccine work?

Rachit Agarwal, Assistant Professor at the Centre for BioSystems Science and Engineering (BSSE), IISc, and his group has developed a potential sub-unit vaccine candidate that contains only parts of the infectious bacterium to stimulate an immune response.

Sub-unit vaccines have been developed before based on just a handful of proteins from the disease-causing bacteria, but none of them have been effective so far. Dr Agarwal's group, however, decided to use Outer Membrane Vesicles (OMVs), which are spherical membrane-bound particles released by some bacteria, and contain an assortment of proteins and lipids which could induce an immune response against the pathogen.

"They're safer compared to a live bacterium, and since they are membrane-derived, they contain all kinds of antigens," explains Agarwal, the senior author of the paper published in 'Biomaterials Advances'.

What are sub-unit vaccines?

Sub-unit vaccines typically only contain a limited number of antigens -- bacterial proteins that can elicit an immune response in the host. In contrast, OMVs contain a variety of antigens and can induce a better immune response, according to the researchers.

Can OMVs be used in vaccine applications?

Mycobacterium-derived OMVs are usually unstable and come in different sizes, making them unsuitable for vaccine applications. But the OMVs coated on gold nanoparticles (OMV-AuNPs) by the IISc team were found to be uniform in size and stable, the statement said.

The researchers also found that human immune cells showed a higher uptake of OMV-AuNPs than of OMVs or gold nanoparticles alone.

"Producing the OMVs is a complex process, and scaling it up was challenging," says Avijit Goswami, a former post-doctoral fellow at BSSE and one of the first authors of the study.

"To synthesise OMV-AuNPs, the OMVs and the gold nanoparticles are forced together through a 100 nm filter. The OMVs break up in the process and encapsulate the gold nanoparticles," explains Edna George, a former postdoctoral fellow at BSSE, and co-first author of the study.

In the study, immune cells cultured in the lab were treated with OMVs derived from Mycobacterium smegmatis, a related bacterial species that does not cause disease in humans.

In future studies, the team plans to develop gold-coated OMVs derived directly from Mycobacterium tuberculosis and test them on animal models to take the results forward for clinical applications.

"Such efforts could open up new avenues for the development of vaccines for other bacterial diseases as well," IISc said.

New TB vaccines in the offing

India has for some time been working on developing new TB vaccines to increase coverage for adults. Previously, central agencies have said that two years down the line, phase-3 clinical trials of two such candidates are set to conclude by 2024.

Dr Suchit Kamble, a scientist at the ICMR-National AIDS Research Institute (NARI) in Pune, told media earlier in April that the trials to evaluate the efficacy and safety of two TB vaccine candidates -- VPM1002 and Immunovac -- in preventing tuberculosis in healthy household contacts of newly-diagnosed sputum-positive pulmonary TB patients were underway.

What is the need for a TB vaccine?

On World Tuberculosis Day this year, Health Minister Mansukh Mandaviya reaffirmed the government’s commitment to making India tuberculosis–free by 2025 by ensuring access to quality healthcare and advanced treatment. The numbers, however, paint a dark picture so far. The year 2021 witnessed a 19 percent increase in the notification of TB patients in the country from 2020. As per the India TB Report 2022, 19,33,381 TB patients (including new and relapse cases) were notified during 2021.

The tuberculosis-causing bacteria was first discovered in 1882 and has since taken millions of lives worldwide, affecting mostly socially underprivileged and working-class populations across the world. Despite being a preventable and curable disease, there were 2.4 million official cases of TB in 2019 in India while an estimated 9,9 million people contracted the disease worldwide in 2020. India continues to on top of the countries with the highest cases. New tuberculosis vaccines are urgently required to achieve India's goal of TB elimination by 2025.

Factors like lack of awareness and resources, poor infrastructure, increasing drug-resistant cases, poor notification and overall negligence compounded with social stigma against TB in countries like India have long impaired public access to treatment and prevention of TB. A new breakthrough in TB vaccines can help save millions of lives in India and worldwide. 

(With inputs from PTI)