A path towards a Hepatitis C Vaccine

Indian Institute of Science experts have achieved a breakthrough in the development of Hepatitis C vaccine. Indo Australian Biotechnology Fund, Department of Biotechnology, Government of India has supported the project.

Twelve to 18 million people in India are infected by Hepatitis C (HCV), a virus that affects the liver and causes cirrhosis that often leads to hepatocellular carcinoma (HCC) and death. India’s share in the disease burden of the world is quite large given its population of more than one billion.

One would think the easy way would be to pop a pill that makes life easier and the liver okay. There are pills, too. At about 1000 dollars a pill, the amount of money needed for a twelve week course is 84000 dollars. Where the money will come from is anybody’s guess.

Hence, scientists of the world have been trying to develop a vaccine. One shot of an injection and one’s body would be armed with the ammunition needed to kill the enemy as the case is with the polio or the small pox vaccine.

Prof. Saumitra Das and his group at the Indian Institute of Science (IISc), Bengaluru, have shown us the light and have developed a vaccine in the lab. As Dr. Das says, “The path to a vaccine involves testing on a larger animal, then toxicity studies, pre-clinical trials and finally Phase 1 to Phase 4 trials on humans. Only then we can say that the vaccine is working. Those are our future plans, too. There are quite a few hurdles on the way, though.”

The Hepatitis C virus has about six genotypes. It means the virus differs from one another only in tiny sequences of nucleic acids but that is enough to prevent a vaccine that works on say Genotype 1 from working on Genotype 2. The virus also has several sub types which only means more differences.

Anuj Kumar, Soma Das, Ranajoy Mullick and others in the group tried a two-step vaccine. First, they took protein components of the outer shells of the Hepatitis C virus (core and envelope) of Genotype 3, which is prevalent in India. These genes were cloned into an Adenovirus as well as Baculovirus based vectors, made into proteins by human liver cancer cells and insect cells respectively, and these were virus like particles (VLP). The one from Adenovirus was termed as Ad-VLP and the other from Baculovirus was termed as Bac-VLP.

In the next step, they injected the VLPs in a special kind of lab mice along with the core and envelope proteins as final booster. This strategy showed exciting results and elicited good immune response.

Dr. Ranajoy Mullick, Senior Research associate at Das’s Lab says, “The vaccine was able to produce antibodies that can neutralize the virus in the vaccinated host and also generated good cellular immune responses, which makes this an excellent vaccine candidate.”

“At IISc we have both facilities; an insect expression system (the cells from an insect as explained earlier) in Prof. Anjali Anoop Karande’s lab and a mammalian expression system (human liver cells) in Prof. Saumitra Das’ lab,” explains Mr Anuj Kumar, one of the researchers involved in developing the vaccine. “Hence, we were able to generate vaccines using both systems, compare the two and demonstrate that a vaccine developed in a mammalian system is better and can provide better inhibition of HCV.”

Why not a traditional vaccine?

A traditional vaccine would have just involved injecting inactive or killed Hepatitis C viruses into models and waiting for an immune response.

Dr. Soma Das from the group says, “It is not so easy. There are practical difficulties. It is very difficult to produce hepatitis C virus in bulk. The viruses have too many mutations and it would be difficult to elicit an immune response against all the strains. Finally, Hepatitis C infects humans and chimps and not other animals. So, a virus challenge model is very difficult to find where the actual immune response could be tested.”

Indo Australian Biotechnology Fund has supported the project. In parallel, two Australian scientists Prof Eric Gowans from the University of Adelaide and Prof Joseph Torresi from the Austin Hospital in Melbourne are also working on a vaccine against Hepatitis C caused by Genotype 1, which is common in Australia as a part of this Indo-Australian joint effort.

Dr Saumitra Das says, “Future plans include testing on animals. But research on chimps is very expensive and also National Institutes of Health in USA have stopped funding chimp-related work. We will have to test our vaccine on larger animals such as pigs and then progress from there to toxicity studies and eventually to preclinical and clinical trials.”

A paper on the work was published in the third week of December 2015 in the journal Vaccine. The group also includes Prasanna Bhat, Priyanka Lahiri, Ranjitha Tatineni, and Debashree Goswami at the Department of Microbiology and Cell Biology, IISc.

Viruses cannot replicate on their own

A virus is the smallest living organism, with a nucleic acid such as DNA or RNA wrapped within a protein shell. Viruses cannot replicate 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 our immune system recognizes the attack, it begins targeting the infected liver cells and as a consequence, the infected individual can be afflicted with mild to severe liver disorders.

A path towards a Hepatitis C Vaccine-1

How a vaccine works

A vaccine (for example polio) is injected into our body. It contains weakened or attenuated polio viruses that cause our immune system to produce particles called antibodies that are stored in our body. If and when we get attacked by the polio virus in future, these antibodies will swing into action and defeat it. End result is we will never get polio, ever.

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