Post-exposure treatment of cats with mouse-cat chimeric antibodies against feline herpesvirus type 1 and feline calicivirus

In order to confirm the in vivo effectiveness of anti- feline herpesvirus type 1 (FHV-1) mouse-cat chimeric antibody (FJH2), and anti-feline calicivirus (FCV) mouse-cat chimeric antibody (F1D7), cats that had been experimentally infected with FHV-1 or FCV were administered intravenously with the chimeric antibodies, and observed for clinical manifestations. The symptoms due to FHV-1 or FCV infection in the cats administered FJH2 or F1D7 were obviously decreased when compared with those of the non-administered control cats. From these results, it was confirmed that both FJH2 and F1D7 were effective at reducing the appearance of symptoms due to FHV-1 and FCV infection, respectively.     

Use of serologic tests to predict resistance to feline herpesvirus 1, feline calicivirus,and feline parvovirus infection in cats

OBJECTIVE: To determine whether detection of virus-specific serum antibodies correlates with resistance to challenge with virulent feline herpesvirus 1 (FHV-1), feline calicivirus (FCV), and feline parvovirus (FPV) in cats and to determine percentages of client-owned cats with serum antibodies to FHV-1, FCV, and FPV. DESIGN: Prospective experimental study. ANIMALS: 72 laboratory-reared cats and 276 client-owned cats. PROCEDURES: Laboratory-reared cats were vaccinated against FHV-1, FCV, and FPV, using 1 of 3 commercial vaccines, or maintained as unvaccinated controls. Between 9 and 36 months after vaccination, cats were challenged with virulent virus. Recombinant-antigen ELISA for detection of FHV-1-, FCV-, and FPV-specific antibodies were developed, and results were compared with results of hemagglutination inhibition (FPV) and virus neutralization (FHV-1 and FCV) assays and with resistance to viral challenge. RESULTS: For vaccinated laboratory-reared cats, predictive values of positive results were 100% for the FPV and FCV ELISA and 90% for the FHV-1 ELISA. Results of the FHV-1, FCV, and FPV ELISA were positive for 195 (70.7%), 255 (92.4%), and 189 (68.5%), respectively, of the 276 client-owned cats. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that for cats that have been vaccinated, detection of FHV-1-, FCV-, and FPV-specific antibodies is predictive of whether cats are susceptible to disease, regardless of vaccine type or vaccination interval. Because most client-owned cats had detectable serum antibodies suggestive of resistance to infection, use of arbitrary booster vaccination intervals is likely to lead to unnecessary vaccination of some cats.     

Feline Herpesvirus 1 and Mycoplasma spp. Conventional PCR Assay Results From Conjunctival Samples From Cats in Shelters With Suspected Acute Ocular Infections

Signs of ocular infections like discharge and conjunctivitis occur commonly in cats in shelters and feline herpesvirus 1 (FHV-1), Chlamydia felis, Mycoplasma spp, and feline calicivirus (FCV) are thought to be the most common causes. While molecular assays are available to amplify nucleic acids of each of these agents as single tests or in panels, additional information is needed concerning whether the assay results can be used to predict response to treatment. The objectives of this study were to report results for conventional polymerase chain reaction (PCR) assays that amplify nucleic acids of FHV-1, Mycoplasma spp., C. felis, and FCV from cats with signs of acute ocular and upper respiratory infections in an animal shelter and to determine whether the results are associated with treatment responses to topical administration of cidofovir (anti-FHV-1) or oxytetracycline (anti-Mycoplasma spp. and C. felis). Conjunctival samples were collected from both eyes of 60 cats with ocular signs of disease. Total deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) were extracted from each sample and assayed for DNA of FHV-1, Mycoplasma spp., and C. felis and RNA of FCV by conventional PCR assays. Cats were randomized to be administered either oxytetracycline ointment or cidofovir drops in both eyes and a standardized ocular disease score system was used to determine a total ocular score for each cat prior to treatment on Day 0 and on Day 7. Nucleic acids of one or more agents were amplified from one or both eyes from 39 of 60 cats (65%). FHV-1 DNA (21 cats), Mycoplasma spp. DNA (25 cats) or FCV RNA (2 cats) were amplified most commonly. After treatment for 7 days, 32 of 60 cats (53.3%) were considered improved with 27 of 32 cats (84.4%) having ocular scores of 0 (21 cats) or 1 (6 cats). When the results of the FHV-1 PCR assay were compared to cidofovir treatment responses, the positive and negative predictive values of the assay were shown to be 29.4% and 60%, respectively. When the results of the Mycoplasma spp. PCR assay were compared to oxytetracycline treatment responses, the positive and negative predictive values of the assay were shown to be 40% and 38.5%, respectively. The predictive value of conventional PCR assay results for FHV-1 or Mycoplasma spp. DNA was low, suggesting that performing these tests to formulate a treatment protocol has minimal clinical utility in cats with suspected acute ocular infections.     

An etiological investigation of domestic cats with conjunctivitis and upper respiratory tract disease in Japan

Chlamydophila felis (C. felis), feline herpesvirus-1 (FHV-1) and feline calicivirus (FCV) were detected in 39 (59.1%), 11 (16.7%) and 14 (21.2%) cats respectively, from 66 domestic cats presented with conjunctivitis and upper respiratory tract disease (URTD) in 9 prefectures of Japan. Dual and multiple infections were found in 7 (10.6%) cats with both C. felis and FHV-1, 10 (15.2%) cats with both C. felis and FCV, and 1 (1.5%) cat with all three agents. C. felis was isolated from 11 (28.2%) of 39 PCR positive cats. Antigenic difference was found in a 96 kDa protein of our isolates and Fe/145 strain isolated in USA. In conclusion, C. felis is the most common agent of feline conjunctivitis and URTD, and the coinfection with C. felis, FHV-1 and FCV are also common in cats in Japan.     

Feline panleukopenia virus, feline herpesvirus-1, and feline calicivirus antibody responses in seronegative specific pathogen-free cats after a single administration of two different modified live FVRCP vaccines

Two groups of feline panleukopenia virus (FPV), feline calicivirus (FCV), and feline herpesvirus-1 (FHV-1) seronegative cats (five cats per group) were administered one of two modified live feline viral rhinotracheitis, calicivirus, and panleukopenia virus (FVRCP) vaccines and the serological responses to each agent were followed over 28 days. While all cats developed detectable FPV and FCV antibody titers; only two cats developed detectable FHV-1 antibody titers using the criteria described by the testing laboratory. For FPV and FHV-1, there were no differences in seroconversion rates between the cats that were administered the intranasal (IN) FVRCP vaccine and the cats that were administered the parenteral FVRCP vaccine on any day post-inoculation. For FCV, the cats that were administered the IN FVRCP vaccine were more likely to seroconvert on days 10 and 14 when compared to cats that were administered the parenteral FVRCP vaccine.     

Results of molecular diagnostic assays targeting feline herpesvirus-1 and feline calicivirus in adult cats administered modified live vaccines

In this pilot study, 12 adult, gang-housed cats that were known to be previously exposed (n=12) to feline herpesvirus-1 (FHV-1) and/or vaccinated against (n=2) feline calicivirus (FCV) and FHV-1 were randomly assigned to one of two groups of six cats each. Nasal and pharyngeal samples were collected from each cat on days -7, -3, and 0 prior to vaccination and on days 3, 7, 10, 14, 17, 21, and 28 after vaccination with an FHV-1, FCV, and panleukopenia (FVRCP) vaccine developed for intranasal (six cats) or parenteral (six cats) use. FHV-1 DNA was amplified from 1/12 cats (1/69 samples; 1.4%) prior to vaccination and 2/12 cats after vaccination (2/154 samples; 1.3%). FCV RNA was amplified from 2/12 cats (2/69 samples; 2.9%) prior to vaccination and 7/12 cats (12/154 samples; 7.8%) after vaccination. Positive molecular diagnostic assay results for FHV-1 and FCV were uncommon prior to or after vaccination in these cats.     

Feline panleukopenia virus, feline herpesvirus-1 and feline calicivirus antibody responses in seronegative specific pathogen-free kittens after parenteral administration of an inactivated FVRCP vaccine or a modified live FVRCP vaccine

Two groups of feline panleukopenia (FPV), feline calicivirus (FCV) and feline herpesvirus 1 (FHV-1) seronegative kittens (six cats per group) were administered one of two feline viral rhinotracheitis, calcivirus and panleukopenia (FVRCP) vaccines subcutaneously (one inactivated and one modified live) and the serological responses to each agent were followed over 49 days (days 0, 2, 5, 7, 10, 14, 21, 28, 35, 42, 49). While the kittens administered the modified live FPV vaccine were more likely to seroconvert on day 7 after the first inoculation than kittens administered the inactivated vaccine, all kittens had seroconverted by day 14. In contrast, FHV-1 serological responses were more rapid following administration of the inactivated FVRCP vaccine when compared with the modified live FVRCP vaccine. There were no statistical differences between the serological response rates between the two FVRCP vaccines in regard to FCV.     

Detection of virulent feline herpesvirus-1 in the corneas of clinically normal cats

To evaluate the clinically normal feline cornea for the presence of virulent feline herpesvirus-1 (FHV-1), corneas from 31 cats (25 with normal eyes and six with active disease or corneal scarring) euthanased at a shelter were collected. Corneas from two specific pathogen-free cats were included as negative controls. Virus isolation (VI), fluorescent antibody (FA) staining and real-time polymerase chain reaction (rt-PCR) were performed on all samples. The presence or absence of dexamethasone in the media was evaluated for its effect on VI. VI was positive for FHV-1 in six corneas from five cats, all with clinically normal eyes. One cornea was positive for feline calicivirus (FCV) in addition to FHV-1, but only in media that included dexamethasone. Eight corneas were positive on rt-PCR for FHV-1, all from cats with clinically normal eyes. All positive VI samples were confirmed with FA staining. VI and rt-PCR were negative for FHV-1 and FCV in cats with active disease or corneal scarring. Data from this study indicate that virulent FHV-1 and FCV can be present in feline corneas that are clinically normal. Dexamethasone may enhance viral spread through a cell receptor mechanism.     

上海市宠物猫杯状病毒、疱疹病毒及流感病毒的分离与鉴定

为了解上海市猫上呼吸道疾病病例中猫杯状病毒(FCV)、猫疱疹病毒1型(FHV-1)和猫流感病毒(FIV)的感染比例及其遗传变化特点,对上海市冬季53份表现上呼吸道症状宠物猫的眼结膜、口咽和鼻黏膜拭子,进行FCV、FHV-1和FIV分离与鉴定,并对分离的病毒进行遗传进化分析.结果显示:53份样品中,FCV分离率为58.4...     

Feline caliciviral disease: experimental immunoprophylaxis.

An attenuated feline calicivirus (FCV) was administered intramuscularly to specific-pathogen-free cats. Vaccination did not cause signs of illness. Oropharyngeal replication of attenuated FCV was not detected, nor was there evidence of virus transmission to contact-control cats. Antiviral neutralizing antibody was present in the serum of all vaccinated cats 7 days after they were given the 2nd intramuscular dose of immunogen. Vaccinated and control cats were challenge exposed to aerosols of a virulent FCV strain. All controls developed severe pneumonia and died within 7 days after this challenge exposure. In the vaccinated cats, signs of illness were absent or minimal; pulmonary lesions were milder and less extensive than those in the control cats. Feline calicivirus was isolated from ocular, nasal, and oropharyngeal swabbings from both control and vaccinated cats after viral challenge. Results indicate protective immunity to FCV disease can be induced by intramuscular administration of an attenuated FCV.     

Feline herpesvirus ocular disease

Infection by FHV-1 is one of the most common ophthalmic diseases of domestic cats worldwide. Although the usual manifestations are conjunctivitis and keratitis, infection with this virus has been linked to a variety of other ophthalmic syndromes of cats, including keratoconjunctivitis sicca and corneal sequestration. Ocular FHV-1 infection of cats provides a significant diagnostic challenge to the practicing veterinarian because, in chronic cases, antigen detection tests often yield negative results. Although therapy for FHV-1 infections of cats is often difficult, the recent development of nontoxic antiviral drugs that demonstrate considerable efficacy against FHV-1 offers hope for improved therapeutic success in the future.     

Mapping neutralizing and non-neutralizing epitopes on the capsid protein of feline calicivirus

Neutralizing epitopes on feline calicivirus (FCV) capsid protein were mapped using chimeric capsid proteins recombinant between two FCV isolates that do not show any cross-neutralization. The three chimeric proteins examined were expressed in murine L929 cells employing an MVA/T7 vaccinia virus expression system and inoculated into major histocompatibility complex haplotype-matched C3/HN mice. Based on the neutralizing antibody titre the neutralizing epitope(s) could be mapped to the 5' hypervariable region of the E region or potentially to the C region. The epitopes of some non-neutralizing antibodies were mapped with the same chimeric proteins to the regions B or D and F of the FCV capsid protein.     

Mapping Neutralizing and Non‐Neutralizing Epitopes on the Capsid Protein of Feline Calicivirus

Neutralizing epitopes on feline calicivirus (FCV) capsid protein were mapped using chimeric capsid proteins recombinant between two FCV isolates that do not show any cross‐neutralization. The three chimeric proteins examined were expressed in murine L929 cells employing an MVA/T7 vaccinia virus expression system and inoculated into major histocompatibility complex haplotype‐matched C3/HN mice. Based on the neutralizing antibody titre the neutralizing epitope(s) could be mapped to the 5′ hypervariable region of the E region or potentially to the C region. The epitopes of some non‐neutralizing antibodies were mapped with the same chimeric proteins to the regions B or D and F of the FCV capsid protein.     

Detection of feline herpesvirus-specific antibodies and DNA in aqueous humor from cats with or without uveitis.

OBJECTIVE: To determine whether uveitis in cats was associated with intraocular production of feline herpesvirus type 1 (FHV-1)-specific antibodies or with detection of FHV-1 DNA in aqueous humor (AH). ANIMALS: 44 cats with idiopathic uveitis, 29 cats with uveitis attributed to Toxoplasma gondii infection, 13 FHV-1 seropositive cats without uveitis, and 9 FHV-1 seronegative cats without uveitis. PROCEDURE: ELISA were used to detect FHV-1-specific antibodies and total IgG antibodies in serum and AH, and the Goldmann-Witmer coefficient (C-value) for intraocular antibody production was calculated. A polymerase chain reaction assay was used to detect FHV-1 DNA in AH. RESULTS: FHV-1 seroprevalence among cats with uveitis was not significantly different from seroprevalence among cats without uveitis. Intraocular FHV-1 antibodies were never detected in cats without uveitis. Significantly more cats with idiopathic uveitis (22/44) or with toxoplasmic uveitis (11/29) had evidence of intraocular antibody production (C-value > 1) than did cats without uveitis. Only cats with idiopathic uveitis had FHV-1 C-values > 8. Among cats with evidence of intraocular antibody production, cats with idiopathic uveitis had a significantly higher median FHV-1 C-value (9.61) than did cats with toxoplasmic uveitis (2.56). Overall, FHV-1 DNA was detected in AH from 12 cats, 11 of which had uveitis. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that FHV-1 can infect intraocular tissues of cats and that intraocular FHV-1 infection may be associated with uveal inflammation in some cats.     

Prevalence of Chlamydophila felis and feline herpesvirus 1 in cats with conjunctivitis in northern Italy

The prevalence of Chlamydophila felis and feline herpesvirus 1 (FHV-1) infection in cats with conjunctivitis in northern Italy was investigated by conventional polymerase chain reaction (PCR) testing. In cats with conjunctivitis, C felis and FHV-1 were detected in 14 of 70 (20%) and in 23 of 70 (33%) animals, respectively. None of the 35 control cats were positive for C felis, whereas 7 (20%) of these cats were positive for FHV-1. Mixed infections were present in 5 of 70 cats (7%). Cats positive for C felis were significantly younger than control animals (P = .02), whereas no significant age differences were observed between FHV-1-positive cats and control cats (P = .41) or between FHV-1-positive animals and C felis-positive animals (P = .16). Cats sampled during acute-phase conjunctivitis were also investigated for the presence of C felis by conjunctival scrapings. In this acute phase, substantial agreement was found when comparing the results of the 2 methods (K = .80). The association between PCR results and conjunctivitis was evaluated for the 2 pathogens. The presence of C felis was significantly associated with conjunctivitis (P = .004), whereas the detection of FHV-1 did not significantly correlate with the clinical sign (P = .25), suggesting that, by itself. PCR is not suitable for the diagnosis of FHV-1-related conjunctivitis.     

Interaction of acute feline herpesvirus-1 and chronic feline immunodeficiency virus infections in experimentally infected specific pathogen free cats.

Cats with or without chronic feline immunodeficiency virus (FIV) infection were exposed to feline herpesvirus, type 1 (FHV-1). FIV infected cats became sicker than non-FIV infected cats and required more supportive treatment. However, there were no differences in the length of their illness or in the levels and duration of FHV-1 shedding. FHV-1 infection caused a transient neutrophilia at Day 7 with a rapid return to preinfection levels. The neutrophilia coincided with a transient lymphopenia that was accompanied by a decline in both CD4+ and CD8+ T-lymphocytes. A brief decrease in the CD4+/CD8+ T-lymphocyte ratio occurred at Day 14 in both FIV infected and non-infected cats. This decrease was mainly the result of an absolute and transient increase in CD8+ T-lymphocytes. CD4+ and CD8+ T-lymphocyte numbers and CD4+/CD8+ T-lymphocyte ratios returned to baseline within 4-8 weeks in both FIV infected and non-infected cats. FIV infected cats produced less FHV-1 neutralizing antibodies during the first 3 weeks of infection than non-FIV infected animals. The IgM FHV-1 antibody response was depressed in FIV infected cats whereas the IgG antibody response was unaffected. FHV-1 infection evoked a comparable transient loss of lymphocyte blastogenic responses to concanavalin A and pokeweed mitogen in both FIV infected and non-infected cats. However, response to pokeweed mitogen took longer to return to normal in FIV infected animals. Lymphocytes from FIV infected cats had a greater and more sustained proliferative response to FHV-1 antigen than non-FIV infected cats. The ongoing IgG antibody response to FIV was not affected by FHV-1 infection.     

Clinical and antiviral effect of a single oral dose of famciclovir administered to cats at intake to a shelter

Although famciclovir is efficacious in feline herpesvirus type 1 (FHV-1)-infected cats, effects of a single dose early in disease course have not been reported. In this two part, randomized, masked, placebo controlled study, cats received a single dose of 125 mg famciclovir (n = 43) or placebo (n = 43; pilot study), or 500 mg famciclovir (n = 41) or placebo (n = 40; clinical trial) on entering a shelter. FHV-1 PCR testing was performed, bodyweight and food intake were recorded, and signs of respiratory disease were scored prior to and 7 days following treatment. FHV-1 DNA was detected in 40% of cats in both parts at study entry. In the pilot study, ocular and nasal discharge scores increased from days 1 to 7 in famciclovir and placebo treated cats. Sneezing scores increased and bodyweight decreased in famciclovir-treated cats. The proportion of cats in which FHV-1 DNA was detected increased over time in all cats in the pilot study. In the clinical trial, food intake and median clinical disease scores for nasal discharge and sneezing increased from days 1 to 7 in both groups and demeanor scores worsened in famciclovir-treated cats. The proportion of cats shedding FHV-1 DNA was greater on day 7 than on day 1 in cats receiving 500 mg famciclovir. A single dose of famciclovir (125 or 500 mg) administered at shelter intake was not efficacious in a feline population in which 40% were already shedding FHV-1.     

Immunisation with a combination of two complementary feline calicivirus strains induces a broad cross-protection against heterologous challenges

Feline calicivirus (FCV) is characterised by a high degree of antigenic variation potentially compromising vaccine efficacy. Inclusion of several FCV strains or antigens in current vaccines could be a means to improve protection against antigenically distinct isolates. This study evaluated the synergy between two FCV strains (FCVG1 and FCV431) by comparing immunity induced by either strain with that provided by a combination of the two strains against an heterologous challenge with antigenically distant FCV strains (FCV393 and FCV220). Thirty-two SPF kittens were randomly allocated to four groups of eight cats in each group. Groups B, C and D cats were vaccinated once subcutaneously with strains FCVG1, FCV431, and FCVG1 + FCV431, respectively. Each kitten received a total dose of 10(3.4) CCID50 of FCV. Control group A was not immunised. On day 31, four cats from each group were challenged oronasally with FCV220 and four cats with FCV393. Following challenge, the cats were monitored for clinical signs, viral shedding and antibody responses. FCV220 and FCV393 induced severe clinical signs in control cats typical of FCV infection. Immunisation with both strains mixed together induced higher neutralizing antibody titres against FCV220 and FCV393 strains on average. Protection was observed in all groups, however combination of the two strains resulted in a better clinical protection and reduction of virus shedding after heterologous challenge. A moderate correlation was observed between neutralizing antibody titres at the time of challenge and protection against clinical signs. These results indicated that vaccines combining antigens from different FCV strains may induce a broader heterologous protection.