Modified-Live Feline Calicivirus Vaccination Reduces Viral RNA Loads, Duration of RNAemia, and the Severity of Clinical Signs after Heterologous Feline Calicivirus Challenge

Abstract

Feline calicivirus (FCV) is a common cat virus causing clinical signs such as oral ulcerations, fever, reduced general condition, pneumonia, limping and occasionally virulent-systemic disease. Efficacious FCV vaccines protect against severe disease but not against infection. FCV is a highly mutagenic RNA virus whose high genetic diversity poses a challenge in vaccine design. The use of only one modified-live FCV strain over several decades might have driven the viral evolution towards more vaccine-resistant variants. The present study investigated the clinical signs, duration, and amount of FCV shedding, RNAemia, haematological changes and acute phase protein reaction in SPF cats after subcutaneous modified-live single strain FCV vaccination or placebo injection and two subsequent oronasal heterologous FCV challenge infections with two different field strains. Neither clinical signs nor FCV shedding from the oropharynx and FCV RNAemia were detected after vaccination. After the first experimental infection, vaccinated cats had significantly lower clinical scores, less increased body temperature and lower acute phase protein levels than control cats. The viral RNA loads from the oropharynx and duration and amount of RNAemia were significantly lower in the vaccinated animals. No clinical signs were observed in any of the cats after the second experimental infection. In conclusion, FCV vaccination was beneficial for protecting cats from severe clinical signs, reducing viral loads and inflammation after FCV challenge.

Modified-Live Feline Calicivirus Vaccination Elicits Cellular Immunity against a Current Feline Calicivirus Field Strain in an Experimental Feline Challenge Study

“…However, the crossprotection against FCV-induced disease in the absence or with low levels of heterologous antibodies has been shown previously [17][18][19][20], and cell-mediated immune mechanisms also play a role in vaccine immunity. The unvaccinated cats did not develop antibodies against F9, which confirms our finding that the vaccine virus was not shed in an amount that was detectable by RT-PCR [28], ruling out the potential for inadvertent immunisation of the unvaccinated cats.…”

“…Furthermore, innate immune mechanisms, such as antiviral factor MX1 and perforin and granzyme B mRNA transcription levels, were elevated in vaccinated cats compared to control cats after vaccination with the modified-live FCV F9 vaccine. The data describing the clinical manifestations of FCV infection in the vaccinated and the control cats as well as the FCV shedding, the FCV RNAemia, the FCV loads, the haematological changes, and the inflammation have been described previously [ 28 ].…”

“…After the first challenge with a current FCV field strain (FCV 273; FCV Challenge I), an adaptive immune response was detected in vaccinated cats with higher absolute numbers of T-cells (CD5), cytotoxic T-cells (CD8) and regulatory T-cells (CD4/CD25), and higher mRNA transcription levels of perforin and granzyme B compared to placebo-vaccinated and challenged control cats. Of note, after FCV Challenge I, the vaccinated cats showed less severe clinical signs, shed less FCV RNA from the oropharynx, and FCV RNA in blood was detected over a shorter duration compared to the control cats [ 28 ]. The first experimental infection with FCV 273 induced humoral and cellular crossimmunity against the second challenge virus, the field strain FCV 27, in all cats, but vaccinated cats still had more IFN-γ-releasing PBMCs upon stimulation with FCV 27 before FCV Challenge II with FCV 27 compared to placebo-vaccinated control cats.…”

“…The leukocyte population was brought into focus based on forward and side scatter, and 10,000 events were acquired. The absolute number of each lymphocyte subset was calculated by multiplying the absolute lymphocyte number assessed in haematology [ 28 ] with the lymphocyte subset percentage as previously published [ 41 ]. The gating strategy consisted of all leukocytes, all lymphocytes, single cells, live cells, and FITC/PE or PE/APC or SSC-A/FITC or SSC-A/PE.…”

“…The study setup is described in detail in Spiri et al (2019) [27], and Spiri et al (2021) [28]. Briefly, ten SPF cats were divided in two groups: five cats (cat ID: JJG4, JJG6, JJH3, JJI1, and JJI2) were vaccinated subcutaneously twice 21 days apart at 15 and 18 weeks of age using a MLV trivalent vaccine containing FCV F9, and five cats (cat ID: JJF1, JJG3, JJH2, JJI3, and JJI4) served as a control group and received a placebo injection (FCV Vaccination I).…”