The rabies virus (RV) fusion protein technology is being used to produce safe and effective vaccines for multiple disease indications. This technology involves a RV in which the N or G gene is fused to a foreign protein antigen gene, such as that from bacteria, a virus or a cancer cell, producing a fusion protein. The specific vaccine can be either that of the Ribonucleoprotein in which the N fusion protein is incorporated, or the killed virus in which the foreign is expressed on the virus surface via the G fusion protein. The company is initially applying this vaccine technology to the development of biodefense-related products, Anthrax vaccine and Botulinum vaccine.
Rabies virus as a carrier for foreign proteins.
Rhabdoviruses are able to incorporate a broad variety of foreign viral and cellular glycoproteins into RV virions. A foreign protein presented in a rigid, multimeric, and highly concentrated way will result in a strong B-cell response. For example, soluble RV G protein is a poorly immunogenic whereas RV G protein presented on a viral particle is highly immunogenic. Additionally, the N and G proteins contained in the virions should provide the necessary T-helper responses to maintain a long-term humoral immune response. We believe that this strong immune response should also apply to a foreign protein expressed in the RV virions
Rationale for Rabies Virus as a vaccine vector
The following properties make RV an ideal candidate as a delivery vaccine vector for various antigens:
- Inactivated rabies virus has been used to vaccinate humans since 1978 and, thusly has a significant history of efficacy and safety.
- The genetic manipulation of RV is possible and several investigators have developed techniques that allow the generation of stable recombinant RVs expressing foreign proteins.
- The RV genome is highly flexible and allows for the expression of multiple foreign genes up to 6.5 kb. In addition, foreign proteins can be incorporated into RV virions and/or fused to the RV nucleoprotein.
- Recombinant RV virions and ribonucleoproteins (RNPs) are easy to purify and highly immunogenic. RV N protein is an excellent B-cell antigen.
- Killed RV virion-based vaccines are produced in large quantities by different companies in the U.S. and new RV based vaccine could easily be produced in existing pipelines.
- Killed RV vaccines are well tolerated and side effects are rare in humans.
- Recombinant RV virions and RNPs are highly stable ensuring the long-term presentation of antigens to the immune system.
- RV induced immune responses are long-lasting.
- Deactivated (killed) RV virions and RNP have been shown to induce strong humoral responses against the foreign antigens without adjuvant.