Development of a bivalent vaccine against hepatitis B and C viruses – HEPATIBIVAX

The approach is to produce subviral particles made with chimeric HBV-HCV envelope proteins. These particles resemble those of the HBV vaccine (they can be purified in the same way) but have the advantage to also contain the entire HCV envelope proteins E1 and E2.

Subviral particles formed by the chimeric HBV-HCV envelope proteins induce in immunized animals antibodies that are able to neutralize in vitro different HCV genotypes. Furthermore, they induce a response against HBV, equivalent to the response induced by a commercial HBV vaccine. This suggests that such particles could replace current vaccines against HBV while providing the additional benefit of protection against HCV. Another major advantage of this approach is that this vaccine could be produced by the same procedures established for HBV vaccines, reducing the time and cost of its industrial development.

It is necessary to consolidate the proof of concept of this vaccine candidate with an appropriate animal model. However, except the chimpanzee, no animal can be infected by these viruses. We will therefore use a mouse model with humanized immune system and liver. These mice will be immunized with the vaccine candidate and challenged by the two viruses to study whether they are protected from infection by both viruses.

This concept of a bivalent vaccine is currently protected by a patent in international stages. If satisfactory results are obtained with this project, an industrial partner will be sought to develop the vaccine through a licensing agreement.

With more than 170 million people worldwide chronically infected by the hepatitis C virus (HCV), and 3 to 4 million new infections occurring each year, there is an urgent need for a prophylactic vaccine against this virus. HCV envelope proteins E1 and E2 constitute a potential target for the development of a prophylactic vaccine as they are involved in virus-host interactions and antibodies directed against these proteins may neutralize HCV. However, these proteins are difficult to produce and purify, requiring the use of processes incompatible with industrial developments. The hepatitis B virus (HBV) is another important human pathogen inducing severe chronic liver diseases. However, the infection by this virus can be prevented using a safe, efficient vaccine established since the early 80’. This vaccine is based on the remarkable property of the small (S) HBV envelope protein to self-assemble in subviral empty envelope particles. We have designed chimeric HBV-HCV envelope proteins containing the entire HCV E1 and E2 sequence that are efficiently assembled into subviral particles and that can be easily purified. This strategy could lead to the development of a bivalent HBV-HCV prophylactic vaccine candidate of potential interest as the populations at risk of infection with these two viruses are essentially the same. Another important advantage of this approach is that the vaccine candidate could be produced with the same industrial procedures used for the HBV vaccine, reducing the time and cost for its industrial development. Our invention is covered by a patent validated in international phases in major countries. This grant proposal is requested to further validate the proof-of-concept of this vaccine in animal models, including the model of mice bearing a humanized liver and immune system, before licensing this innovative technology to an industrial partner.