Development of a new veterinary subunit vaccine against rabies

Abstract

Rabies is a fatal zoonotic viral disease that affects several species of mammals. The virus is transmitted to humans mainly by rabid dogs, causing at least 55,000 human deaths each year mainly in Africa and Asia. Mass vaccination of dogs has been the mainstay of successful canine rabies control. Currently available vaccines are expensive and require intensive immunization and booster schemes to maintain protective immunity. The rabies virus glycoprotein (RVGP) is the antigen responsible for the induction of neutralizing antibodies by the host immune system, protecting it against viral infection. An adjuvant that would increase the immunogenicity of the vaccine and allow for a reduction of numbers of doses would thus be very useful to reduce the cost and vaccine failures due to incomplete vaccinations. Immuno-stimulating complexes (ISCOMs) are spherical, cage-like adjuvant particles composed of cholesterol, phospholipid and saponins (derived from the tree Quillaja saponaria) which are held together by hydrophobic interactions, steric factors and hydrogen bonds. ISCOM adjuvant possesses efficient antigen delivery and immune stimulating properties that in combination with recombinant G protein may be good for the generation of an adequate immune response. Uniquely among vaccines, those for rabies can be given both pre and post exposure to virus. This is principally through the development of neutralizing antibodies. A high level of neutralizing antibodies correlates essentially to protection against rabies, capable of stop infection before its spread. Although veterinary rabies vaccines are available and free in many places, there is an important fault coverage due to the need of constant boosters, which leads many owners to stop vaccinating their pets and cattle. Having this in mind, the development of new vaccines against rabies should aim increase the interval between booster doses, or even facilitating the administration process. The purpose of this research is to develop a prototype vaccine based on the use of a recombinant glycoprotein from rabies virus envelope. We intend to use RVGP combined with different adjuvants and the use of different routes of immunization in animal model, verifying the levels of protection. Obtaining a new formulation for the prevention of canine rabies may generate an innovative new vaccine, especially if it is effective by oral route. (AU)