Pathogenicity and immunogenicity of gI/gE/TK-gene-deleted Felid herpesvirus 1 variants in cats

Abstract

Background Felid herpesvirus 1 (FHV-1) is a major pathogenic agent of upper respiratory tract infections and eye damage in felines worldwide. Current FHV-1 vaccines offer limited protection of short duration, and therefore, do not reduce the development of clinical signs or the latency of FHV-1. Methods To address these shortcomings, we constructed FHV ∆gIgE-eGFP, FHV ∆TK mCherry, and FHV ∆gIgE/TK eGFP-mCherry deletion mutants (ΔgI/gE, ΔTK, and ΔgIgE/TK, respectively) using the clustered regularly interspaced palindromic repeats (CRISPR)/CRISP-associated protein 9 (Cas9) system (CRISPR/Cas9), which showed safety and immunogenicity in vitro. We evaluated the safety and efficacy of the deletion mutants administered with intranasal (IN) and IN + subcutaneous (SC) vaccination protocols. Cats in the vaccination group were vaccinated twice at a 4-week interval, and all cats were challenged with infection 3 weeks after the last vaccination. The cats were assessed for clinical signs, nasal shedding, and virus-neutralizing antibodies (VN), and with postmortem histological testing. Results Vaccination with the gI/gE-deleted and gI/gE/TK-deleted mutants was safe and resulted in significantly lower clinical disease scores, fewer pathological changes, and less nasal virus shedding after infection. All three mutants induced virus-neutralizing antibodies after immunization. Conclusions In conclusion, this study demonstrates the advantages of FHV-1 deletion mutants in preventing FHV-1 infection in cats.

The CDE region of feline Calicivirus VP1 protein is a potential candidate subunit vaccine

“…Pathogens are destroyed by mucosal NAbs and sIgA upon first invasion, thereby preventing subsequent infection [ 44 ]. Several studies have demonstrated the efficacy of combined subcutaneous and intranasal immunization with feline herpesvirus, another major respiratory pathogen [ 45 – 47 ]. After systemic immunity is established by subcutaneous immunization, an intranasal booster immunization is administered to enhance local mucosal immunity [ 47 ].…”

“…Several studies have demonstrated the efficacy of combined subcutaneous and intranasal immunization with feline herpesvirus, another major respiratory pathogen [ 45 – 47 ]. After systemic immunity is established by subcutaneous immunization, an intranasal booster immunization is administered to enhance local mucosal immunity [ 47 ]. The limitation of this study is that we did not further explore the best immune program for accessing the CDE subunit vaccine.…”

First report of molecular epidemiology and phylogenetic characteristics of feline herpesvirus (FHV-1) from naturally infected cats in Kunshan, China

“…The whole genome of feline herpesvirus is approximately 135 kb, consisting of a unique long (UL) and unique short (US) gene sequences. US gene is flanked by a pair of identical inverted repeats, called terminal short repeats (TRs) and inverted short repeats (IRs) [ 8 – 11 ]. There is only one serotype for all FHV-1 isolates.…”