Generating an Attenuated Feline Infectious Peritonitis (FIP) Vaccine by Inactivating EndoU
Principal Investigator: Gary Whittaker
DESCRIPTION (provided by applicant):
Feline infectious peritonitis (FIP) is a lethal systemic infection of cats caused by a feline coronavirus. FIP is considered to be one of the most significant infectious diseases in feline medicine. Although there have been many attempts to generate either a killed virus or live-attenuated virus vaccine, to date these attempts have been unsuccessful. We recently showed that mutation of a highly conserved coronavirus protein, termed EndoU results in highly attenuated virus that induces a robust interferon response, and that vaccination with this mutant virus protects mice from a lethal coronavirus challenge in a mouse hepatitis virus model. Based on these findings, we propose to generate and evaluate an EndoU mutant of serotype I feline coronavirus (FIPV Black), for evaluation as an attenuated vaccine. We will generate this virus using reverse genetics and evaluate it in feline macrophages to determine if the mutant feline CoV induces interferon and apoptosis. The goal of this 1-year study is to generate the virus and evaluate the innate immune response to the virus in cell culture. Future studies will determine if the mutant virus is capable of inducing a protective immune response to FIPV in animal models.