Chronic hepatitis C virus (HCV) infection represents a major health threat to the global population. In India, approximately 15 to 20 per cent of cases of chronic liver diseases are caused by the HCV infection.

Although new drugs hold great promise for HCV eradication in infected individuals, the treatment is highly expensive. Scientists from the Indian Institute of Science (IISc), Bengaluru, have now developed a vaccine customised for the Indian population, which has shown promising results in preclinical studies.

According to estimates, HCV has infected approximately 170 million people globally and there are around 6 to 12 million of them in India. Approximately 20 per cent of patients with an acute HCV infection can clear the virus, which majorly depends on the host's immune response.

This virus, which spreads by direct contact with the blood of an infected person, can cause severe liver complications, which may lead to cancer. Among the many strains of the virus, HCV genotype 3a (gt3a) is the predominant strain found in the Indian sub-continent.

Professor Saumitra Das and his team from IISc have developed a vaccine for HCV genotype 3a. This work was funded by research grants from the Indo-Australian Biotechnology Fund (IABF), department of biotechnology, Government of India. The findings have been published recently in the journal 'Vaccine'.

A virus is the smallest living organism, with a genetic code such as DNA or RNA wrapped within a protein shell. Viruses cannot function on their own and need to find a suitable host cell in which they proliferate. In case of HCV, the virus finds its home in human liver cells. It then begins using the liver cell machinery to make copies of itself. When the immune system recognises such an intrusion, it begins attacking the infected liver cells and as a consequence, the infected individual can be afflicted with mild to severe liver disorders.

Several preclinical trials of virus-like particle (VLP)-based vaccine strategies are in progress throughout the world. In the present study, the researchers have generated gt3a hepatitis C virus-like particles (HCV-LP). According to the researchers, the vaccine in this case is a "molecular cocktail of virus-like particles that mimics HCV along with a bio-engineered adenovirus vector (viral vectors are tools commonly used by molecular biologists to deliver genetic material into cells), encoding the core and envelope proteins of HCV". In this work, the researchers inserted those genes of HCV into the adenovirus vector so that it would provoke the immune system to produce neutralising antibodies against the hepatitis C virus.

The use of VLP along with HCV protein boost has shown exciting results. Not only was the vaccine able to produce antibodies that neutralise the virus in the vaccinated host, but also generated good cellular immune responses, which makes this an excellent vaccine candidate. "Our results suggest that the combined regimen of HCV-LP followed by the HCV core and envelope protein boost could be a more effective strategy of HCV vaccination," said Dr Das.

Since the HCV vaccine challenge model is not available till date, the next stage of the research work involves testing the vaccine immunogenicity in higher animals (such as pig) before it reaches clinical trials.

The VLP-based vaccine was developed using both an insect expression system and an adenovirus-based expression system. After generating vaccines using both systems, the researchers concluded that the VLP vaccine developed in a mammalian system is better and can provide more protection against HCV.

WORKING OF THE VACCINE

The researchers are proposing a two-step vaccination approach against HCV. In the first instance, the host is primed with virus-like particles (VLPs). VLPs in this case are protein components of the outer shell of the virus, which include the core and envelope proteins assembled together to resemble the virus.

These VLPs are recognised by the host as foreign agents and the immune system produces antibodies or neutralising antibodies against it. Some of the antibody producing cells are then stored in the body as memory cells for a speedy defence in case of future attacks.

After a couple of doses of VLPs, stage two of the vaccine is delivered, which is the bio- engineered adenovirus-producing HCV core and envelope structural proteins.

In this case, the researchers inserted the structural genes of HCV into the adenovirus vector. The modified adenovirus serving as part two of the vaccine regimen would begin production of HCV shell proteins inside the host. This further provokes the immune system to produce neutralising antibodies against it. The antibodies against the HCV shell proteins are stored as memory providing the individual with the perfect defence in case HCV enters the body in the near future.

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