Researchers at IISc develop novel method to deliver vaccine candidate for TB
The Indian Institute of Science (IISc), Centre for BioSystems Science and Engineering, has designed a new method to deliver a vaccine candidate for tuberculosis (TB). The research involves using spherical vesicles secreted by bacteria coated on gold nanoparticles which can then be delivered to the immune cells. This, according to the researchers, can potentially trigger an immune response and offer protection against the disease.
Annually, the deadly Tuberculosis caused by the bacterium mycobacterium affects and succumbs over a million people. The only effective vaccine currently in use is the BCG vaccine. It contains a weakened form of the disease-causing bacterium. When injected into the bloodstream, it triggers the production of antibodies that can help fight the disease, said IISc.
While the BCG vaccine works well in children, it is not as effective at protecting adolescents and adults. This encouraged Rachit Agarwal, assistant professor, Centre for BioSystems Science and Engineering, IISc, and his team to develop a potential subunit vaccine candidate that contains only parts of the infectious bacterium to stimulate an immune response. The research paper was published in Biomaterials Advances.
According to IISc, in the past its researchers had developed subunit vaccines based on merely a handful of proteins from the bacteria causing the disease, which were found to be ineffective in controlling the infection which was seen to recur and cause fatality.
We opted to use Outer Membrane Vesicles (OMVs). These 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, said Agarwal adding that it was safer compared to a live bacterium. What is derived from the membrane contains all kinds of antigens.
Subunit 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.
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 researchers also found that human immune cells showed a higher uptake of OMV-AuNPs than of OMVs or gold nanoparticles alone, said Agarwal who is also the senior author of the paper published in Biomaterials Advances.
Avijit Goswami, a former postdoctoral fellow at BSSE and one of the first authors of the study noted that producing the OMVs is a complex process, and scaling it up was challenging.
In order 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,” stated Edna George, 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, said Agarwal.
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