Limited efficacy of an inactivated feline immunodeficiency virus vaccine.
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Animals↗
Biomedical subjects
O Jarrett
Publications and source records attributed to O Jarrett.
Persistence and transmission of natural type I feline coronavirus infection.
To examine the mode of natural transmission and persistence of feline coronavirus (FCoV), FCoV strains shed by domestic cats were investigated over periods of up to 7 years. An RT-PCR that amplified part of the 3' end of the viral spike (S) gene was devised to distinguish FCoV types I and II. All but 1 of 28 strains of FCoV from 43 cats were type I. Nucleotide identities of the amplified 320 bp product from 49 type I FCoVs ranged from 79 to 100 %. The consensus partial S sequence of isolates recovered from persistently infected cats at time intervals spanning years was generally conserved. While most cats were infected with a single strain, a few may have been infected by more than one strain. Cats that were transiently infected and ceased shedding could be re-infected with either the same, or a different, strain. In most cases, whether a cat became persistently or transiently infected was independent of the virus strain. However, one strain was unusual in that it infected the majority of cats in the household simultaneously and was still being shed 18 months later. Factors that influence whether FCoV establishes lifelong infection in some cats and not others are determined mainly by the host response to infection.
Animals↗
Dynamics of viral and proviral loads of feline immunodeficiency virus within the feline central nervous system during the acute phase following intravenous infection.
Animal models of human immunodeficiency virus 1, such as feline immunodeficiency virus (FIV), provide the opportunities to dissect the mechanisms of early interactions of the virus with the central nervous system (CNS). The aims of the present study were to evaluate viral loads within CNS, cerebrospinal fluid (CSF), ocular fluid, and the plasma of cats in the first 23 weeks after intravenous inoculation with FIV(GL8). Proviral loads were also determined within peripheral blood mononuclear cells (PBMCs) and brain tissue. In this acute phase of infection, virus entered the brain in the majority of animals. Virus distribution was initially in a random fashion, with more diffuse brain involvement as infection progressed. Virus in the CSF was predictive of brain parenchymal infection. While the peak of virus production in blood coincided with proliferation within brain, more sustained production appeared to continue in brain tissue. In contrast, proviral loads in the brain decreased to undetectable levels in the presence of a strengthening PBMC load. A final observation in this study was that there was no direct correlation between viral loads in regions of brain or ocular tissue and the presence of histopathology.
Animals↗
Protection against oronasal challenge with virulent feline leukaemia virus lasts for at least 12 months following a primary course of immunisation with Leukocell 2 vaccine.
The duration of immunity provided by a feline leukemia virus (FeLV) vaccine, Leukocell 2, was determined. Kittens were vaccinated when 9 and 12 weeks of age and were challenged 12 months later with FeLV-A/Glasgow-1. An oronasal challenge protocol without corticosteroid enhancement was developed in order to induce a persistent viraemia in a high proportion of adult cats. Fourteen of 18 (80%) of the vaccinated cats challenged in this way remained non-viraemic while 9/15 (60%) of age-matched controls became persistently infected, a preventable fraction of 63%. This difference was statistically significant (P=0.038). For comparison, 10 of 12 (83%) 15-17-week-old kittens challenged in the same way became persistently infected, confirming the relative resistance of adult animals to FeLV. Tests for virus neutralising and anti-feline oncornavirus-associated cell membrane antigen (FOCMA) antibodies suggested that the former were more important than the latter in protection. Thus, Leukocell 2 protected a significant proportion of cats from FeLV challenge 1 year after primary vaccination as kittens.
Animals↗
Feline leukaemia virus neutralising antibodies.
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Animals↗
Prevalence of bovine immunodeficiency virus infection in cattle in Great Britain.
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Animals↗
Comparison of six in-house tests for the rapid diagnosis of feline immunodeficiency and feline leukaemia virus infections.
Six rapid tests for the diagnosis of feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) infections which have recently been introduced in Europe for use in small animal practice were compared. Eight hundred serum samples were tested and those reacting FIV-positive in at least one of the tests were confirmed by Western blot, and those reacting FeLV-positive were confirmed by virus isolation. The specificity and sensitivity of each test and the quality of the results produced were compared.
Animals↗
Use of a reverse-transcriptase polymerase chain reaction for monitoring the shedding of feline coronavirus by healthy cats.
The pattern of shedding of feline coronavirus (FCoV) was established in 155 naturally infected pet cats from 29 households over periods of up to five years. Viral RNA was detected in faeces by reverse-transcriptase PCR (RT-PCR), and plasma antiviral antibodies by immunofluorescence. The cats rarely shed FCoV in their saliva. Three patterns of FCoV shedding were observed. Eighteen of the cats shed virus continuously, so were persistent, and possibly lifelong, carriers; none of them developed feline infectious peritonitis. Fifty-six cats ceased shedding virus, although they were susceptible to reinfection, and 44 shed intermittently or were being continuously reinfected. Four of the cats were resistant to infection. Seventy-three per cent of the virus shedding episodes lasted up to three months and 95 per cent up to nine months. There was a correlation between shedding and antibody titre but the cats could remain seropositive for some time after they had ceased shedding virus. One-off testing for FCoV by RT-PCR is inappropriate. Identification of longterm carriers requires that a positive result be obtained by RT-PCR on faecal samples for at least eight consecutive months. A cat should be shown to be negative over five months, or to have become seronegative, to ensure that it has ceased shedding virus.
Animals↗
Feline leukemia virus DNA vaccine efficacy is enhanced by coadministration with interleukin-12 (IL-12) and IL-18 expression vectors.
The expectation that cell-mediated immunity is important in the control of feline leukemia virus (FeLV) infection led us to test a DNA vaccine administered alone or with cytokines that favored the development of a Th1 immune response. The vaccine consisted of two plasmids, one expressing the gag/pol genes and the other expressing the env gene of FeLV-A/Glasgow-1. The genetic adjuvants were plasmids encoding the feline cytokines interleukin-12 (IL-12), IL-18, or gamma interferon (IFN-gamma). Kittens were immunized by three intramuscular inoculations of the FeLV DNA vaccine alone or in combination with plasmids expressing IFN-gamma, IL-12, or both IL-12 and IL-18. Control kittens were inoculated with empty plasmid. Following immunization, anti-FeLV antibodies were not detected in any kitten. Three weeks after the final immunization, the kittens were challenged by the intraperitoneal inoculation of FeLV-A/Glasgow-1 and were then monitored for a further 15 weeks for the presence of virus in plasma and, at the end of the trial, for latent virus in bone marrow. The vaccine consisting of FeLV DNA with the IL-12 and IL-18 genes conferred significant immunity, protecting completely against transient and persistent viremia, and in five of six kittens protecting against latent infection. None of the other vaccines provided significant protection.
Adjuvants, Immunologic↗
Long-term impact on a closed household of pet cats of natural infection with feline coronavirus, feline leukaemia virus and feline immunodeficiency virus.
A closed household of 26 cats in which feline coronavirus (FCoV), feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) were endemic was observed for 10 years. Each cat was seropositive for FCoV on at least one occasion and the infection was maintained by reinfection. After 10 years, three of six surviving cats were still seropositive. Only one cat, which was also infected with FIV, developed feline infectious peritonitis (FIP). Rising anti-FCoV antibody titres did not indicate that the cat would develop FIP. The FeLV infection was self-limiting because all seven of the initially viraemic cats died within five years and the remainder were immune. However, FeLV had the greatest impact on mortality. Nine cats were initially FIV-positive and six more cats became infected during the course of the study, without evidence of having been bitten. The FIV infection did not adversely affect the cats' life expectancy.
Animals↗
Factors influencing cellular immune responses to feline immunodeficiency virus induced by DNA vaccination.
Virus-specific effector cytotoxic T lymphocytes (CTL) were elicited in the peripheral blood of domestic cats following a single intramuscular inoculation of replication defective feline immunodeficiency virus proviral DNA (FIVDeltaRT). Higher levels of virus-specific cytolysis were observed in the blood when cats were co-inoculated with feline gamma-interferon (IFN) DNA. The responses declined by 12 weeks following the first DNA inoculation and were, with the exception of FIV Gag-specific responses in some cats, refractory to repeated DNA inoculations. Nevertheless, a significant proportion of the cats were protected from challenge with homologous virus. The effects of interval between inoculations, route of DNA delivery, and promoter used to regulate viral gene expression on the induction of virus-specific CTLs were evaluated. The highest levels of virus-specific lysis were recorded following intramuscular co-inoculation of FIVDeltaRT and gamma-IFN DNA, where FIV gene expression was under the control of a cytomegalovirus (CMV) promoter. However, the highest levels of protection were observed using the viral 5'LTR as the promoter. These results suggest that a single intramuscular inoculation of FIVDeltaRT DNA together with gamma-IFN DNA may be sufficient to induce virus-specific CTLs and protection.
Animals↗
Feline leukaemia virus: protective immunity is mediated by virus-specific cytotoxic T lymphocytes.
Feline leukaemia virus (FeLV) nucleic acid vaccination of domestic cats affords protection against viraemia and the development of latency without inducing antiviral antibodies.1 To determine the contribution of cell-mediated immunity to the control of virus replication and clearance from the host, FeLV-specific cytotoxic T lymphocyte (CTL) responses were compared in vaccine-protected, transiently viraemic, and persistently viraemic cats. Vaccinal immunity was associated with the detection of higher levels of virus-specific effector CTL in the peripheral blood and lymphoid organs to FeLV Gag/Pro and Env antigens than those observed in unvaccinated control, persistently viraemic cats (P<0.001). Likewise, higher levels of virus-specific CTLs were also observed in transiently viraemic cats which recovered following exposure to FeLV. In cats that controlled their infection, recognition of Gag/Pro antigens was significantly higher than the recognition of Env antigens. This is the first report highlighting the very significant role that virus-specific CTL have in determining the outcome of FeLV infection in either vaccinated cats or cats recovering naturally from FeLV exposure.
Animals↗
Vaccination with inactivated virus but not viral DNA reduces virus load following challenge with a heterologous and virulent isolate of feline immunodeficiency virus.
It has been shown that cats can be protected against infection with the prototypic Petaluma strain of feline immunodeficiency virus (FIV(PET)) using vaccines based on either inactivated virus particles or replication-defective proviral DNA. However, the utility of such vaccines in the field is uncertain, given the absence of consistent protection against antigenically distinct strains and the concern that the Petaluma strain may be an unrepresentative, attenuated isolate. Since reduction of viral pathogenicity and dissemination may be useful outcomes of vaccination, even in the absence of complete protection, we tested whether either of these vaccine strategies ameliorates the early course of infection following challenge with heterologous and more virulent isolates. We now report that an inactivated virus vaccine, which generates high levels of virus neutralizing antibodies, confers reduced virus loads following challenge with two heterologous isolates, FIV(AM6) and FIV(GL8). This vaccine also prevented the marked early decline in CD4/CD8 ratio seen in FIV(GL8)-infected cats. In contrast, DNA vaccines based on either FIV(PET) or FIV(GL8), which induce cell-mediated responses but no detectable antiviral antibodies, protected a fraction of cats against infection with FIV(PET) but had no measurable effect on virus load when the infecting virus was FIV(GL8). These results indicate that the more virulent FIV(GL8) is intrinsically more resistant to vaccinal immunity than the FIV(PET) strain and that a broad spectrum of responses which includes virus neutralizing antibodies is a desirable goal for lentivirus vaccine development.
Animals↗
Strategies of retrovirus survival in the cat.
Retroviruses establish persistent infections in their hosts which often lead to serious and fatal diseases after a long incubation period. The molecular basis of this persistence is the integration of a copy of the viral genome into cellular chromosomal DNA. At the level of the whole animal, however, each retrovirus genus has evolved a different strategy to ensure its survival. This variety is well illustrated in the cat. Feline leukaemia virus, an oncovirus, has a simple genomic structure and survives in its host by suppressing the immune response to the virus. As a result, this virus is antigenically highly conserved. By contrast, feline immunodeficiency virus and feline foamy virus, representatives of the lentiviruses and spumaviruses, respectively, have more complex genomes which include genes responsible for maintaining the virus in a latent state thereby avoiding elimination in the face of a powerful antiviral immune response. In the lentiviruses, this response drives the selection of viruses exhibiting variation in antigenicity and pathogenicity.
Animals↗
Analysis of the protective immunity induced by feline immunodeficiency virus vaccination.
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Animals↗
Suppression of feline immunodeficiency virus replication in vitro by a soluble factor secreted by CD8+ T lymphocytes.
Mitogen-activated lymphoblasts isolated from the blood and lymph nodes, but not the spleen, of domestic cats acutely infected with the Petaluma or Glasgow8 isolates of feline immunodeficiency virus (FIV), suppressed the replication of FIV in the MYA-1 T-cell line in a dose-dependent manner. This effect was not limited to the homologous isolate of FIV. The suppressor activity declined with progression to chronic infection, with lower levels of activity detectable only in the lymph nodes. Immunization of domestic cats with whole inactivated FIV vaccine elicited profound suppressor activity in both the blood and lymph nodes. The suppressor activity was associated with the CD8+ T-cell subpopulation, the effect did not appear to be major histocompatibility complex-restricted, and was mediated by a soluble factor(s). This activity may be associated with the control of virus replication during both the asymptomatic stages of FIV infection, and in the protective immunity observed in cats immunized with whole inactivated virus vaccines.
Acute Disease↗
The antibody response of cattle infected with bovine immunodeficiency virus to peptides of the viral transmembrane protein.
The development of the antibody response to peptides of the transmembrane glycoprotein of bovine immunodeficiency virus (BIV) was followed over a period of 50 weeks in six cattle experimentally infected with the BIV(FL112) isolate. Antibody was detected by an enzyme immunoassay using either a linear or a cyclized peptide with structural features common to an immunodominant region of other lentiviruses. The assay was specific for BIV, detecting antibody in bovine sera to BIV(FL112) or BIV(R29) but not to six other common viruses of cattle. Antibody was present in the sera of all cattle inoculated with BIV(FL112) within 4 weeks of infection, peaked between 10 and 30 weeks and persisted in most cattle during the 50 weeks of observation. These features indicate that this assay may be useful in identifying cattle infected with other strains of BIV in the field.
Amino Acid Sequence↗
Feline viruses in wildcats from Scotland.
Few data are available on the prevalence of feline viruses in European wildcats (Felis silvestris). Previous surveys have indicated that wildcats may be infected with the common viruses of domestic cats, apart from feline immunodeficiency virus (FIV). In the present study, 50 wildcats trapped throughout Scotland (UK) between August 1992 and January 1997 were tested for evidence of viral infection. All were negative for FIV by several serological or virological methods. By contrast, 10% of the cats were positive for feline leukemia virus (FeLV) antigen and infectious virus was isolated from 13% of a smaller subset. Of the wildcats tested for respiratory viruses, 25% yielded feline calicivirus (FCV) and although no feline herpesvirus was isolated, 16% of the samples had neutralizing antibodies to this virus. Antibodies to feline coronavirus (FCoV) were found in 6% of samples. Feline foamy virus (FFV) was an incidental finding in 33% of samples tested. This study confirms that wildcats in Scotland are commonly infected with the major viruses of the domestic cat, except for FIV.
Animals↗