Temporally separated feline calicivirus isolates do not cluster phylogenetically and are similarly neutralised by high-titre vaccine strain FCV-F9 antisera in vitro

OBJECTIVES: Feline calicivirus (FCV) is a highly variable and globally important feline pathogen for which vaccination has been the mainstay of control. Here, we test whether the continued use of FCV-F9, one of the most frequently used vaccine strains globally, is driving the emergence of vaccine-resistant viruses in the field. METHODS: This study made use of two representative panels of field isolates previously collected from cats visiting randomly selected veterinary practices across the UK as part of separate cross-sectional studies from 2001 and 2013/2014. Phylogenetic analysis and in vitro virus neutralisation tests were used to compare the genetic and antigenic relationships between these populations and FCV-F9. RESULTS: Phylogenetic analysis showed a typically radial distribution dominated by 52 distinct strains, with strains from both 2001 and 2013/2014 intermingled. The sequence for FCV-F9 appeared to be integral to this phylogeny and there were no significant differences in the genetic distances within each studied population (intra-population distances), or between them (inter-population distances), or between each population and FCV-F9. A 1 in 8 dilution neutralised 97% and 100% of the 2001 and 2013/14 isolates, respectively, and a 1 in 16 dilution neutralised 87% and 75% of isolates, respectively. There was no significant difference either in variance between the FCV-F9 neutralising titres for the two populations, or in the distribution of neutralisation titres across the two populations. CONCLUSIONS AND RELEVANCE: Although FCV is a highly variable virus, we found no evidence for a progressive divergence of field virus from vaccine strain FCV-F9, either phylogenetically or antigenically, with FCV-F9 antisera remaining broadly and equally cross-reactive to two geographically representative and temporally separated FCV populations. We suggest this may be because the immunodominant region of the FCV capsid responsible for neutralisation may have structural constraints preventing its longer term progressive antigenic evolution.