How Virus-Like Particles will help combat disease

Be it the case of commonly known diseases such as malaria and tuberculosis, or the recent outbreaks of Ebola and Zika, the body’s exact mechanisms of immune defence are often complex and poorly understood.

Due to a combination of ethical issues and practical limitations, traditional vaccines are going out of favour, and Virus-Like Particles (VLPs) have emerged as attractive new options to combat disease. VLPs are formed by the self-assembly of viral proteins into structures that mimic the shape, size, structure, and surface properties of natural viruses. They have a wide range of scaffolds and epitopes (the part of an antigen that is recognised by the immune system), and have a proven potential to induce immunity.

Diagrammatic representation of a virus and its VLPs. Native viruses consist of genomic DNA/RNA enclosed within a capsid composed of structural proteins. When expressed recombinantly, many of these proteins spontaneously self-assemble into nucleic acid free VLPs which resemble the native virus.

Maanya Gaur, a researcher with the IITB-Monash Research Academy, is working on a project involving such Virus-like Particles under the supervision of Prof Santosh Noronha, Dr Lizhong He, and Prof Wei Shen. The Academy, a Joint Venture between IIT Bombay and Monash University, operates a graduate research program in Mumbai. Research is conducted by scholars in both countries, whilst studying for a dually-badged PhD from both organisations.

Explains Maanya, “Virus-like particles are increasingly being used as scaffolds to develop novel subunit vaccines. My work involves evaluating the B. subtilis expression system to produce VLPs that can be used as vaccine candidates. Since this organism has a high capacity for protein secretion, we will focus on engineering and optimizing it as a safer and more economical platform for the production of VLPs. The secretion of VLPs directly into the culture medium will simplify the process of vaccine production and reduce the cost of downstream processing and purification.”

A pathogen is something that causes disease, like a virus. ‘Antigenic’ is the capacity of a chemical structure to bind specifically with a group of certain products that have adaptive immunity, while ‘immunogenic’ refers to the ability of a substance to provoke an immune response in the body of a human or animal.

Traditional vaccines are comprised of attenuated (weakened) or inactivated pathogens and have been immensely successful against diseases such as poliomyelitis and smallpox, but not against other important ones like AIDS and malaria. On the other hand, newer subunit vaccines use defined antigenic components and are safer, but not immunogenic enough to confer complete protection against disease. The ‘prime-boost’ strategy, which involves administering different types of subunit vaccines to induce a diverse range of immune responses, is generally required.

“This is precisely why we need to enhance the repertoire of safer, more effective vaccines, says Maanya. “At the same time, production processes need to be kept simple and economical.”

Says Prof Murali Sastry, CEO, IITB-Monash Research Academy, “Virus-like particles are now increasingly being engineered as scaffolds for the display of heterologous antigens and also for enzyme immobilization. However, the major challenge is to develop strategies which can make VLP technology safer and more economical, which is crucial for acceptance in developing countries. And this is where researchers like Maanya could make a vital difference. As the reputation of the IITB-Monash Research Academy begins to grow and as more organisations start collaborating with The Academy, we anticipate that the Academy will contribute to maintaining India’s reputation as a leading-edge global research hub.”

Maanya is hoping that her work will lead to the production of safe and affordable VLPs. We’re confident she will succeed.

Research scholar: Maanya Gaur, IITB-Monash Research Academy

Project title: Studies on the Production of Virus-Like Particles (VLPs) in Bacillus subtilis.

Supervisors: Prof Santosh Noronha, Dr Lizhong He, Prof Wei Shen

Contact details:

This story was written by Mr Krishna Warrier based on inputs from the research student and IITB-Monash Research Academy. Copyright IITB-Monash Research Academy.