Structure-Based Design of a Novel Subunit Immunogen for Development as a Feline Infectious Peritonitis (FIP) Vaccine
Principal Investigator: Gary Whittaker
DESCRIPTION (provided by applicant):
Feline infectious peritonitis (FIP) is a lethal systemic infection of cats caused by a feline coronavirus, and is commonly considered to be the most significant infectious disease in feline medicine. It is currently without viable therapeutic options. The most effective medical intervention for FIP is likely to be by vaccination, and there have been many attempts to develop vaccines against FIP. However, to date these attempts have proven to be unsuccessful. All coronaviruses have a prominent envelope glycoprotein on their surface; called spike (S), which is the major antigenic determinant and is also responsible for receptor binding and membrane fusion during virus entry. There are two functional domains within S – a “head” (receptor-binding domain) and a “stalk” (fusion domain). Recently, the cryo-electron microscopy structure of a coronavirus spike has highlighted the critical importance of a major neutralizing epitope which is exposed on the stalk, and which comprises the key domains (including the fusion peptide) previously identified in the Whittaker lab. Most vaccination strategies against viruses have focused on the variable “head” domain of the envelope protein, however more recently, novel “stalk”-based vaccination approaches have become established e.g. for influenza virus and paramyxoviruses. The advantages of stalk-based immunity are likely to be shared with coronaviruses. Based on these findings, we consider that a subunit vaccine comprising the feline coronavirus stalk, and including the exposed domains that comprise the conserved fusion peptide and major neutralizing epitope, is an excellent candidate for immunization against FIP.