Mucosal and systemic immune correlates of protection against feline enteric coronavirus infection

Abstract

Feline infectious peritonitis (FIP) is a disease with high mortality that results from a mutation in the genome of the relatively harmless and ubiquitous feline coronavirus (FCoV) (Licitra, Millet et al. 2013). FIP causes a deadly effusive and/or granulomatous disease in cats (Kipar, May et al. 2005). Because FIP is always fatal, our aim is to aid with the development of a vaccine against the parent virus FCoV. The goal of this study is to complete a comprehensive assessment of the mucosal immune response associated with FCoV infection and clearance. Previous research has shown that cats infected with FCoV can clear the virus, or they can become intermittent or persistent virus shedders (Marks 2016). It is thought that rapid waning of the humoral immune response predisposes cats to reinfection (Myrrha, Silva et al. 2011). A closed cat colony with circulating FCoV infection was studied longitudinally to assess mucosal immune correlates of protection. Blood and fecal samples were collected monthly and colonic biopsies were obtained at an arbitrary time 0. Virologic assessment included PCR detection of virus in feces and colonic tissue. Immunological assessment included FECV-specific serum IgG and fecal IgA. Lamina propria lymphocytes from colon biopsies were phenotyped using flow cytometry and were assessed for FCoV-specific IgA and IFNγ expression by ELISPOT. Expression of IL17 and FoxP3 was measured by qRT-PCR. Although histopathology of colonic biopsies from cats shedding virus was unremarkable, an inflammatory state was indicated by total IgA producing cells, IFNγ production, and increased IL17:FoxP3. FCoV-specific IgA was also associated with viral shedding. Taken together, results indicate mucosal and systemic antibody responses are responsible for limiting FECV infection while cell-mediated responses were not detected. Therefore, a vaccine strategy targeting antibody induction via a mucosal route may provide protection against FECV infection.