It remains to be determined how some cats are protected from developing FIP. It has been suggested that cats developing a successful CMI response do not develop FIP, whereas cats that develop a predominantly humoral response are likely to develop disease [Pedersen 1987]. Hypergammaglobulinaemia [Ward et al, 1974; Paltrinieri et al, 1998] is common in cats with FIP. Also a profound depletion of T cells from the blood [de Groot-Mijnes et al, 2005] as well as from lymphoid tissues has been described [Haagmans et al, 1996; Paltrinieri et al, 2003; Dean et al 2003].
As in coronavirus infections of other species, maternally derived antibody (MDA) usually gives protection until about 5-6 weeks of age [Addie & Jarrett, 1992]. Levels of MDA decline and become undetectable by 6-8 weeks of age [Pedersen et al 1981].
Cats that did not develop disease after experimental coronavirus infection displayed a greater CMI compared to those that did develop disease [Pedersen & Floyd, 1985, de Groot-Mijnes et al, 2005]. Studies that measured cytokine responses in blood or lymphatic tissues revealed decreased IL-12 responses, and low levels of IFN-gamma expression [Kiss et al, 2004; Gelain et al 2006; Kipar et al 2006], indicative of impaired cellular immune responses, although results were not always consistent.
Cats may be reinfected only weeks after they have overcome a first episode of feline coronaviruses because natural immunity is short-lived. [Addie et al, 2003].
The role of humoral immunity in protection against FIP is controversial. Clearance of natural infections has been associated with antibodies directed against the FCoV spike protein [Gonon et al, 1999], suggesting that, in natural infection, humoral immunity may have a role in protection. However, the role of humoral immunity in natural infections is unknown. It has been proposed that antibodies, especially those directed against the spike protein, can be detrimental. In cats with pre-existing antibodies an enhanced form of disease has occurred in experimental infections, typified by an earlier development of disease and a shortened disease course leading to a more rapid death. This phenomenon was observed in experimental cats that acquired their antibodies through passive or active immunization [Pedersen & Boyle 1980; Weiss & Scott 1981]. Furthermore, in a study in which cats were immunised with a recombinant vaccinia virus expressing the coronaviral S protein, cats became severely ill 7 days after challenge with the virulent, FIP-causing mutant. In contrast, the unvaccinated control cats survived for more than 28 days [Vennema et al, 1990]. This antibody-dependent enhancement (ADE) is likely mediated by opsonisation of the virus facilitating viral uptake by macrophages via Fc receptor-mediated attachment [de Groot and Horzinek, 1995; Corapi et al, 1992]. However, the role of ADE in natural infection is not clear since in field studies cats were most likely to develop FIP on first exposure to FCoV [Addie et al, 1995a, 1995b, 2003].