RESUMO
Flea allergy dermatitis (FAD) is considered a harmful and persistent allergic disease in cats, dogs and humans. Effective and safe antigen-specific treatments are lacking. Previously we reported that the simultaneous co-immunization with a DNA vaccine and its cognate coded protein antigen could induce antigen-specific iTreg cells (inducible Treg cells); demonstrating its potential to protect animals from FAD in a murine model. Its clinical efficacy however, remains to be demonstrated. In this report, we clinically tested this protocol to treat established FAD in cats following flea infestations. We present data showing a profound therapeutic improvement of dermatitis in these FAD cats following two co-immunizations, not only in relieving clinical symptoms, but also the amelioration of the allergic responses, including antigen-induced wheal formation, elevated T cell proliferation, infiltration of lymphocytes and migration of mast cells to the sites. This study demonstrates that a co-immunization approach as described can be used to treat flea-induced allergic disease in animals, thus implicating its potential for a practical clinical application.
Assuntos
Doenças do Gato/terapia , Dermatite Alérgica de Contato/veterinária , Ectoparasitoses/veterinária , Sifonápteros/patogenicidade , Vacinas de DNA/imunologia , Transferência Adotiva , Animais , Doenças do Gato/imunologia , Gatos , Proliferação de Células , Dermatite Alérgica de Contato/imunologia , Dermatite Alérgica de Contato/terapia , Ectoparasitoses/imunologia , Ectoparasitoses/terapia , Feminino , Ativação Linfocitária , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Sifonápteros/imunologia , Linfócitos T Reguladores/imunologiaRESUMO
The duration of immunity of the dual-subtype feline immunodeficiency virus (FIV) vaccine, Fel-O-Vax FIV, for protection against subtype-B FIV was assessed in this study. Vaccinated cats along with controls were challenged with FIV(FC1), a subtype-B FIV strain, 54 weeks after the final vaccination, and monitored for 46-48 weeks for provirus and viral RNA in peripheral blood, provirus in lymphoid organs, and CD4:CD8 ratios. Results of provirus detection in peripheral blood and lymphoid organs and plasma viral RNA loads showed that 10/14 vaccinated cats were fully protected for 48 weeks against infection with FIV(FC1) whereas 5/5 controls were persistently infected with FIV(FC1). CD4:CD8 inversions were noted in association with FIV infection and viral loads were not significantly different between FIV infected controls and the unprotected vaccinated animals.
Assuntos
Doenças do Gato/prevenção & controle , Vírus da Imunodeficiência Felina/imunologia , Infecções por Lentivirus/veterinária , Vacinas Virais , Análise de Variância , Animais , Anticorpos Antivirais/sangue , Relação CD4-CD8/veterinária , Doenças do Gato/imunologia , Doenças do Gato/virologia , Gatos , Primers do DNA , Ensaio de Imunoadsorção Enzimática/veterinária , Eutanásia Animal , Feminino , Vírus da Imunodeficiência Felina/genética , Vírus da Imunodeficiência Felina/isolamento & purificação , Infecções por Lentivirus/prevenção & controle , Linfonodos/virologia , Masculino , Provírus/genética , Provírus/imunologia , Provírus/isolamento & purificação , RNA Viral/sangue , Organismos Livres de Patógenos Específicos , Carga Viral/veterináriaRESUMO
Allergen-induced immediate hypersensitivity (AIH) is a health issue of significant concern. This robust inflammatory reaction is initiated by the allergen-specific T cell responsiveness. Severe lesion reactions on skin are consequential problem requiring medical treatment. Effective Ag-specific treatments or preventions are lacking. Using a rodent model of AIH induced by flea allergens, we first report that coimmunization of DNA and protein vaccines encoding the flea salivary specific Ag-1 ameliorated experimental AIH, including Ag-induced wheal formation, elevated T cell proliferation, and infiltration of lymphocytes and mast cells to the site of allergen challenge. The amelioration of AIH was directly related to the induction of a specific population of flea antigenic specific T cells exhibiting a CD4(+)CD25(-)FoxP3(+) phenotype, a characteristic of regulatory T (T(REG)) cells. These T(REG) cells expressing IL-10, IFN-gamma, and the transcriptional factor T-bet after Ag stimulation were driven by a tolerogenic MHC class II(+)/CD40(low) dendritic cell population that was induced by the coimmunization of DNA and protein vaccines. The tolerogenic dendritic cell could educate the naive T cells into CD4(+)CD25(-)FoxP3(+) T(REG) cells both in vitro and in vivo. The study identified phenomenon to induce an Ag-specific tolerance via a defined Ag vaccinations and lead to the control of AIH. Exploitation of these cellular regulators and understanding their induction provides a basis for the possible development of novel therapies against allergic and related disorders in humans and animals.
Assuntos
Alérgenos/imunologia , Hipersensibilidade Imediata/imunologia , Sifonápteros/imunologia , Linfócitos T Reguladores/imunologia , Vacinas Combinadas/imunologia , Vacinas de DNA/imunologia , Animais , Células Dendríticas/imunologia , Modelos Animais de Doenças , Feminino , Hipersensibilidade Imediata/prevenção & controle , Hipersensibilidade Imediata/terapia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Linfócitos T Reguladores/metabolismoRESUMO
West Nile virus (WNV) is a mosquito borne, neurotropic flavivirus that causes a severe central nervous system (CNS) infection in humans and animals. Although commercial vaccines are available for horses, none is currently approved for human use. In this study, we evaluated the efficacy and mechanism of immune protection of two candidate WNV vaccines in mice. A formalin-inactivated WNV vaccine induced higher levels of specific and neutralizing antibodies compared to a DNA plasmid vaccine that produces virus-like particles. Accordingly, partial and almost complete protection against a highly stringent lethal intracranial WNV challenge were observed in mice 60 days after single dose immunization with the DNA plasmid and inactivated virus vaccines, respectively. In mice immunized with a single dose of DNA plasmid or inactivated vaccine, antigen-specific CD8(+) T cells were induced and contributed to protective immunity as acquired or genetic deficiencies of CD8(+) T cells lowered the survival rates. In contrast, in boosted animals, WNV-specific antibody titers were higher, survival rates after challenge were greater, and an absence of CD8(+) T cells did not appreciably affect mortality. Overall, our experiments suggest that in mice, both inactivated WNV and DNA plasmid vaccines are protective after two doses, and the specific contribution of antibody and CD8(+) T cells to vaccine immunity against WNV is modulated by the prime-boost strategy.
Assuntos
Anticorpos Antivirais/sangue , Linfócitos T CD8-Positivos/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia , Febre do Nilo Ocidental/imunologia , Febre do Nilo Ocidental/prevenção & controle , Vírus do Nilo Ocidental/imunologia , Animais , Anticorpos Antivirais/imunologia , Especificidade de Anticorpos , Antígenos CD8/genética , Imunização Secundária , Injeções Intramusculares , Injeções Intraperitoneais , Camundongos , Camundongos Congênicos , Camundongos Endogâmicos C57BL , Testes de Neutralização , Plasmídeos , Vacinas de DNA/administração & dosagem , Vacinas de DNA/imunologia , Febre do Nilo Ocidental/sangueRESUMO
Most studies of the cytokine response to influenza virus infection have been carried out in human, porcine and murine models, however the data available on equine cytokines is limited. An experimental challenge study was undertaken in unvaccinated naïve horses and horses vaccinated with a commercial inactivated influenza vaccine. The humoral antibody response to vaccination and virus challenge was measured by single radial haemolysis (SRH) assay and clinical signs of influenza and viral shedding were monitored post-challenge. Levels of three equine pro-inflammatory cytokines interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha and the antiviral cytokine interferon (IFN)-alpha were examined by quantitative RT-PCR of mRNA. Vaccination provided significant clinical and virological protection and resulted in a significant reduction of IFN-alpha and IL-6 expression on day 2 post-challenge. The patterns of cytokine expression observed in control animals suffering from influenza after challenge are comparable to those reported in studies of other species.
Assuntos
Citocinas/biossíntese , Doenças dos Cavalos/imunologia , Vírus da Influenza A Subtipo H3N8/imunologia , Vacinas contra Influenza/imunologia , Infecções por Orthomyxoviridae/imunologia , Animais , Anticorpos Antivirais/sangue , Citocinas/genética , Feminino , Cavalos , Imunodifusão/métodos , Masculino , Infecções por Orthomyxoviridae/fisiopatologia , RNA Mensageiro/biossíntese , Distribuição Aleatória , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Índice de Gravidade de Doença , Vacinas de Produtos Inativados/imunologia , Eliminação de Partículas ViraisRESUMO
A study was conducted to evaluate efficacy of inactivated, reverse genetics-based H5N3 avian influenza vaccines and the predictive ability of a vaccination/serology model for testing vaccine batches. Serologic response, protection against mortality, and protection against viral shedding from trachea and cloaca were assessed for vaccines prepared varying only in antigen content. When the birds were grouped according to serologic response, a clear association with protection could be seen. In general, for birds possessing a nonmeasurable titer (< 10), mortality after challenge was a near certainty. Low titers of 10 to 40 resulted in the prevention of mortality but not viral shedding. Titers greater than 40 prevented mortality and reduced viral shedding. The results suggest that a test model including vaccination of chickens at 3 wk, bleeding at 6 wk, and quantitative assessment of serologic response by using a standardized hemagglutination inhibition assay system can be an excellent predictor of vaccine efficacy.
Assuntos
Galinhas/virologia , Vacinas contra Influenza/imunologia , Influenza Aviária/prevenção & controle , Animais , Técnicas Genéticas , Virus da Influenza A Subtipo H5N1/imunologiaRESUMO
H5N1 avian influenza viruses are continuing to spread in waterfowl in Eurasia and to threaten the health of avian and mammalian species. The possibility that highly pathogenic (HP) H5N1 avian influenza is now endemic in both domestic and migratory birds in Eurasia makes it unlikely that culling alone will control H5N1 influenza. Because ducks are not uniformly killed by HP H5N1 viruses, they are considered a major contributor to virus spread. Here, we describe a reverse genetics-derived high-growth H5N3 strain containing the modified H5 of A/chicken/Vietnam/C58/04, the N3 of A/duck/Germany/1215/73, and the internal genes of A/PR/8/34. One or two doses of inactivated oil emulsion vaccine containing 0.015 to 1.2 microg of HA protein provide highly efficacious protection against lethal H5N1 challenge in ducks; only the two dose regimen has so far been tested in chickens with high protective efficacy.
Assuntos
Galinhas/imunologia , Patos/imunologia , Virus da Influenza A Subtipo H5N1/imunologia , Vacinas contra Influenza/imunologia , Influenza Aviária/imunologia , Influenza Aviária/prevenção & controle , Animais , Galinhas/virologia , Cloaca/virologia , Relação Dose-Resposta Imunológica , Patos/virologia , Vacinas contra Influenza/administração & dosagem , Influenza Aviária/virologia , Especificidade da Espécie , Organismos Livres de Patógenos Específicos , Traqueia/virologia , Eliminação de Partículas ViraisRESUMO
Clinically normal horses developed cellular immunity to Sarcocystis neurona following IM vaccination with a commercial killed S. neurona vaccine, as indicated by the development of measurable anti-S. neurona IgG antibodies and additional intradermal skin testing. Large-scale independent assessments of the vaccine's performance and safety are in progress under field conditions. The next step in the evaluation of this vaccine would be to attempt experimental challenge after a reproducible reliable equine model of S. neurona encephalitis has been established that allows for reisolation of the pathogen after challenge.
Assuntos
Anticorpos Antiprotozoários/imunologia , Encefalite/veterinária , Doenças dos Cavalos/prevenção & controle , Vacinas Protozoárias , Sarcocystis/imunologia , Sarcocistose/veterinária , Animais , Encefalite/prevenção & controle , Feminino , Técnica Indireta de Fluorescência para Anticorpo/veterinária , Doenças dos Cavalos/imunologia , Cavalos , Testes Intradérmicos/veterinária , Masculino , Sarcocistose/prevenção & controle , Resultado do TratamentoRESUMO
Fel-O-Vax FIV is an inactivated virus vaccine designed as an aid in the prevention of infection of cats, 8 weeks or older, by feline immunodeficiency virus (FIV). It contains two genetically distinct FIV strains. The efficacy of this vaccine was demonstrated in a vaccination-challenge study designed to meet various regulatory requirements for registering the vaccine. Eight-week-old kittens were vaccinated with an immunogenicity vaccine which contained minimal release levels of FIV antigens formulated with a proprietary adjuvant system. Twelve months later, all vaccinates and controls were challenged with a heterologous FIV strain. Following the vigorous challenge exposure, cats were monitored for FIV viremia. It was found that 16% of the vaccinated cats developed viremia while 90% of the controls became persistently infected with FIV, which demonstrated that the vaccine was efficacious and the protective immunity lasted for at least 12 months. The safety of the vaccine was demonstrated by a field safety trial in which only 22 mild reactions of short duration were observed following administering 2051 doses of two pre-licensing serials of Fel-O-Vax FIV to cats of various breeds, ages and vaccination histories. Thus, Fel-O-Vax FIV is safe and efficacious for the prevention of FIV infection in cats.