Efficacy of a bivalent inactivated non-adjuvanted feline calicivirus vaccine: Relation between in vitro cross-neutralization and heterologous protection in vivo
Introduction
Feline calicivirus (FCV) is a major pathogen of the cat, causing a variety of clinical conditions including upper respiratory tract disease [1], [2], chronic stomatitis [3], dermatitis [4] and lameness [5]. Recently, outbreaks of virulent systemic disease (VSD) have been reported in North America [6], [7], [8] and Europe [9], and are characterized by a high rate of mortality, even in vaccinated cats. Despite vaccination, prevalence of FCV infection in the cat population remains high [1].
FCV is a single-stranded positive sense RNA virus, characterized by a strong genetic variability and antigenic diversity [10], [11], [12], [13]. The humoral immune response plays a critical role in the protection against FCV-induced disease, and the E region of the capsid protein is a major target of neutralizing antibodies [14], [15]. This area is subdivided into the 5′ and 3′ hypervariable regions, separated by a short relatively conserved domain [16]. These hypervariable areas contain the immunodominant antigenic sites and have been shown to be under positive selection [17], [18].
Immunofluorescence profiles with monoclonal antibodies mapped in region E and sequencing of the capsid protein have highlighted the antigenic diversity of FCV [13]. Cross-neutralization has been used to compare variants, and in particular, to evaluate the ability of vaccine strains to protect against circulating antigenic variants [13], [19], [20].
To improve cross-protection, two strains with broad cross-antigenicity have been selected [21] and used to develop an inactivated non-adjuvanted bivalent vaccine (PUREVAX®1 RCPCh-FeLV). The selection of the vaccine strains was based on cross-neutralization studies. The objective of this study was to assess the relation between cross-neutralization in vitro and protection in vivo in experimental conditions. This is also the first demonstration of the efficacy of a vaccine against multiple heterologous FCV challenges.
Section snippets
Vaccine
Cats were vaccinated with a bivalent inactivated non-adjuvanted FCV vaccine combined with other feline antigens (same components as PUREVAX RCPCh-FeLV vaccine). The calicivirus antigen consisted of inactivated concentrated purified virus particles, derived from two different strains (FCV431 and FCVG1) and combined in equal amounts. The vaccine was not adjuvanted. A group of non-vaccinated cats was used as control.
In studies Nos. 1 and 2, another group of cats was vaccinated with the reference
Homology of region E between FCVG1, FCV431 and other strains
At the amino acid level, homology of region E between the nine strains included in the analysis ranged from 61% to 75% (Table 1). The divergence within region E between FCV431 or FCVG1 and the various challenge strains (FCV255, 33585, ENVT, 91-11 and 91-25) ranged from 28% to 37%.
The phylogenetic analysis of the amino acids sequence of region E confirmed the strong antigenic diversity of FCV. FCV33585 and FCV-ENVT but not FCV100869 clustered with other VS-FCV strains (Fig. 1). The analysis
Discussion
Despite vaccination, FCV is still a major infectious disease of cats, and conditions like VSD or chronic stomatitis pose a serious problem to veterinarians. One of the reasons for the high prevalence of FCV infection is the inability of vaccines, whatever the technology, to prevent infection [23], [24], [25], [26]. Even vaccines aiming at inducing a strong local immunity, like feline herpesvirus or spumavirus-vectored vaccines, have a limited efficacy [23], [25]. Currently, most commercially
Conclusion
This study was the first report on the vaccinal protection against several heterologous FCV strains, including VS-FCV strains. It showed that cross-neutralization is a relevant technique to select FCV vaccine strains. For this vaccine, cross-neutralization was predictive of a significant protection against FCV, including a reduction in the severity of VSD. This method made it possible to select FCV strains with broad cross-reactivity and to develop a vaccine affording protection against a large
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