Hepatitis C is an infectious viral disease of the liver that if untreated, could lead to cirrhosis and even liver cancer. The World Health Organization (WHO) estimates that approximately 500,000 people die each year from Hepatitis C and associated complications. The Hepatitis C virus (HCV) has several distinct genetic variants (or genotypes), which makes it difficult to characterise, and vaccine design against the virus has proved to be extremely challenging. Taking up this challenge head on are the research teams of Saumitra Das, Professor, Department of Microbiology and Cell Biology, and Anjali Anoop Karande, Professor, Department of Biochemistry, from the Indian Institute of Science (IISc), Bangalore.
Das is also collaborating with researchers from Australia and spearheading the effort to develop a successful Hepatitis C vaccine, and is funded by the Indo-Australian Biotechnology Fund (IABF) from the Department of Biotechnology (Govt. of India). “The issues are bilateral and the interests are overlapping,” said Das.
The typical design strategy of a vaccine, is to use weakened or heat-killed forms of the disease-causing microorganism (pathogen), or a pathogen moiety/toxoid that is sufficient to trigger an immune reaction from the body without actually causing the disease symptoms. This primes the body, forms memory of the pathogen and launches a full-on second immune reaction when it encounters the same pathogen again, thereby preventing the disease from manifesting. However, for a long time, no infectious cell culture system was available for HCV. Also, the lack of a suitable small animal model affected the progress in HCV vaccine research.
This scenario called for an alternative vaccination strategy against HCV and the research team that included graduate student Anuj Kumar, and postdocs Soma Das and Ranajoy Mullick looked closely at the virus’s design. The HCV virus is only about 60 nanometers in diameter and consists of the genetic material (single-stranded, positive sense RNA) enveloped in an external protein coat and some lipid molecules. Instead of using attenuated/heat-killed cultures, the researchers developed virus like particles (VLPs) of HCV. The VLPs are being made by assembling the core and envelop proteins (without the RNA), to resemble the virus. The VLPs are identified by the body as foreign agents and should be sufficient to trigger an immune response. The proposed 2-phase vaccination design would involve administering the VLPs for a couple of doses, and administering adenoviruses containing the structural genes of HCV. Adenoviruses are typically used to insert foreign genetic material and this second strategy would initiate the production of the HCV outer proteins within the body itself and thereby initiate the body’s immune reaction to these proteins.
Initial tests of this vaccination strategy against HCV have been very successful in mice. These mice not only produce antibodies neutralising the virus, but also generate a strong cellular response. If it proves to be successful in other trials, it would make it the first vaccine against the Hepatitis C-3a strain, which is specific to the Indian subcontinent. This work was recently published in Vaccine.
The team is now ready for the next stage of trials in pigs that have an immune system very similar to humans and are looking forward to subsequent human clinical trials of the vaccine. They are also working towards making VLP vaccines more effective, robust and generic to other genotypes. Das feels that this is the right time for industry collaboration and intellectual partners to take the vaccine into methodical pre-clinical trials. He also pointed out the limitations in terms of commercialisation of the product and said, “What is required at the moment is an industry partner with resources, and time. That can help us get the finished product to the Indian population so that people can be vaccinated for a disease that takes almost 10 – 12 years to show its symptoms.”