RÉSUMÉ
The outbreak of clade 2.3.4.4b H5 highly pathogenic avian influenza (HPAI) in North America that started in 2021 has increased interest in applying vaccination as a strategy to help control and prevent the disease in poultry. Two commercially available vaccines based on the recombinant herpes virus of turkeys (rHVT) vector were tested against a recent North American clade 2.3.4.4b H5 HPAI virus isolate: A/turkey/Indiana/22-003707-003/2022 H5N1 in specific pathogen free white leghorn (WL) chickens and commercial broiler chickens. One rHVT-H5 vaccine encodes a hemagglutinin (HA) gene designed by the computationally optimized broadly reactive antigen method (COBRA-HVT vaccine). The other encodes an HA gene of a clade 2.2 virus (2.2-HVT vaccine). There was 100% survival of both chicken types COBRA-HVT vaccinated groups and in the 2.2-HVT vaccinated groups there was 94.8% and 90% survival of the WL and broilers respectively. Compared to the 2.2-HVT vaccinated groups, WL in the COBRA-HVT vaccinated group shed significantly lower mean viral titers by the cloacal route and broilers shed significantly lower titers by the oropharyngeal route than broilers. Virus titers detected in oral and cloacal swabs were otherwise similar among both vaccine groups and chicken types. To assess antibody-based tests to identify birds that have been infected after vaccination (DIVA-VI), sera collected after the challenge were tested with enzyme-linked lectin assay-neuraminidase inhibition (ELLA-NI) for N1 neuraminidase antibody detection and by commercial ELISA for detection of antibodies to the NP protein. As early as 7 days post challenge (DPC) 100% of the chickens were positive by ELLA-NI. ELISA was less sensitive with a maximum of 75% positive at 10DPC in broilers vaccinated with 2.2-HVT. Both vaccines provided protection from challenge to both types of chickens and ELLA-NI was sensitive at identifying antibodies to the challenge virus therefore should be evaluated further for DIVA-VI.
Sujet(s)
Poulets , Sous-type H5N1 du virus de la grippe A , Vaccins antigrippaux , Grippe chez les oiseaux , Animaux , Poulets/virologie , Poulets/immunologie , Grippe chez les oiseaux/prévention et contrôle , Grippe chez les oiseaux/virologie , Grippe chez les oiseaux/immunologie , Sous-type H5N1 du virus de la grippe A/immunologie , Sous-type H5N1 du virus de la grippe A/génétique , Vaccins antigrippaux/immunologie , Vaccins antigrippaux/administration et posologie , Vaccins synthétiques/immunologie , Vaccins synthétiques/administration et posologie , Glycoprotéine hémagglutinine du virus influenza/immunologie , Glycoprotéine hémagglutinine du virus influenza/génétique , Anticorps antiviraux/immunologie , Anticorps antiviraux/sang , Amérique du Nord , Vaccination , Maladies de la volaille/prévention et contrôle , Maladies de la volaille/virologie , Maladies de la volaille/immunologie , Herpèsvirus de type 1 du dindon/immunologie , Herpèsvirus de type 1 du dindon/génétiqueRÉSUMÉ
Marek's disease (MD), caused by the Marek's disease virus (MDV), is a common infectious tumor disease in chickens and was the first neoplastic disease preventable by vaccination. However, the vaccine cannot completely prevent virulent MDV infections, allowing both the vaccine and virulent MDV to coexist in the same chicken for extended periods. This study aims to investigate the changes in viral load of the very virulent strain Md5 and the rHVT-IBD vaccine in different chicken tissues using a real-time PCR assay. The results showed that the rHVT-IBD vaccine significantly reduced the viral load of MDV-Md5 in different organs, while the load of rHVT-IBD was significantly increased when co-infected with Md5. Additionally, co-infection with Md5 and rHVT-IBD in chickens not only changed the original viral load of both viruses but also affected the positive rate of Md5 at 14 days post-vaccination. The positive rate decreased from 100% to 14.29% (feather tips), 0% (skin), 33.33% (liver), 16.67% (spleen), 28.57% (thymus), 33.33% (bursa), and 66.67% (PBL), respectively. This study enhances our understanding of the interactions between HVT vector vaccines and very virulent MDV in chickens and provides valuable insights for the future development of MD vaccines.
Sujet(s)
Poulets , Co-infection , Vaccins contre la maladie de Marek , Maladie de Marek , Maladies de la volaille , Charge virale , Animaux , Maladie de Marek/virologie , Maladie de Marek/prévention et contrôle , Maladie de Marek/immunologie , Poulets/virologie , Co-infection/virologie , Co-infection/médecine vétérinaire , Maladies de la volaille/virologie , Maladies de la volaille/prévention et contrôle , Vaccins contre la maladie de Marek/immunologie , Vaccins contre la maladie de Marek/génétique , Virulence , Herpèsvirus de type 1 du dindon/immunologie , Herpèsvirus de type 1 du dindon/génétique , Vaccins synthétiques/immunologie , Vaccins synthétiques/génétique , Herpèsvirus aviaire de type 2/génétique , Herpèsvirus aviaire de type 2/immunologie , Herpèsvirus aviaire de type 2/pathogénicité , Vaccination , Vecteurs génétiques/génétiqueRÉSUMÉ
Cytokines are co-administrated with vaccines or co-expressed in the vaccine virus genome to improve protective efficacy by stimulating immune responses. Using glycosylphosphatidylinositol (GPI) anchoring by attachment to the target cytokine, we constructed recombinant Marek's disease virus (MDV) vaccine strain 301B/1 (v301B/1-rtg-IL-15) that expresses chicken interleukin-15 (IL-15) as the membrane-bound form at the cell surface. We evaluated the vaccine efficacy of v301B/1-rtg-IL-15 given as a bivalent Marek's disease (MD) vaccine in combination with turkey herpesvirus (HVT) against a very virulent plus MDV strain 648A challenge. The efficacy was compared with that of conventional bivalent MD vaccine, as a mixture with HVT plus parental v301B/1 or v301B/1-IL-15, which expresses a natural form of IL-15. The membrane-bound IL-15 expression did not interfere with the virus growth of recombinant v301B/1-rtg-IL-15. However, the MD incidence in birds vaccinated with v301B/1-rtg-IL-15 was higher than that of birds given the conventional bivalent MD vaccine containing parental v301B/1 virus, although the v301B/1-rtg-IL-15 vaccinated group showed increased natural killer cell activation at day 5 postvaccination, the same day as challenge. Overall, the protection of v301B/1-rtg-IL-15 was not improved from that of v301B/1 against very virulent plus MDV challenge.
Eficacia de una vacuna contra el virus de la enfermedad de Marek cepa 301B/1 recombinante que expresa la interleucina-15 de pollo anclada a la membrana. Las citocinas se administran junto con vacunas o se co-expresan en el genoma del virus de la vacuna para mejorar la eficacia protectora mediante la estimulación de respuestas inmunitarias. Utilizando el anclaje de glicosilfosfatidilinositol (GPI) mediante unión a la citoquina objetivo, se construyó una cepa de vacuna recombinante del virus de la enfermedad de Marek (MDV) 301B/1 (v301B/1-rtg-IL-15) que expresa la interleucina-15 de pollo (IL-15) como la forma unida a la membrana en la superficie celular. Se evaluó la eficacia de la vacuna v301B/1-rtg-IL-15 administrada como vacuna bivalente en combinación con el herpesvirus del pavo (HVT) contra el desafío con un virus muy virulento cepa 648A de la enfermedad de Marek (MD). La eficacia se comparó con la de la vacuna bivalente convencional contra la enfermedad de Marek, como una mezcla con HVT más la cepa v301B/1 parental o con el virus recombinante v301B/1-IL-15, que expresa una forma natural de IL-15. La expresión de IL-15 unida a membrana no interfirió con el crecimiento del virus de v301B/1-rtg-IL-15 recombinante. Sin embargo, la incidencia de la enfermedad de Marek en aves vacunadas con v301B/1-rtg-IL-15 fue mayor que la de las aves que recibieron la vacuna de Marek bivalente convencional que contenía el virus v301B/1 parental, aunque el grupo vacunado con v301B/1-rtg-IL-15 mostró una mayor activación de las células asesinas naturales en el día 5 después de la vacunación, que fue el mismo día del desafío. En general, la protección por la vacuna v301B/1-rtg-IL-15 no mejoró con respecto a la conferida por v301B/1 contra un desafío muy virulento de la enfermedad de Marek.
Sujet(s)
Poulets , Herpèsvirus aviaire de type 2 , Interleukine-15 , Vaccins contre la maladie de Marek , Maladie de Marek , Vaccins synthétiques , Animaux , Interleukine-15/génétique , Interleukine-15/immunologie , Interleukine-15/métabolisme , Maladie de Marek/prévention et contrôle , Maladie de Marek/immunologie , Vaccins contre la maladie de Marek/immunologie , Vaccins contre la maladie de Marek/génétique , Vaccins synthétiques/immunologie , Herpèsvirus aviaire de type 2/génétique , Herpèsvirus aviaire de type 2/immunologie , Maladies de la volaille/prévention et contrôle , Maladies de la volaille/virologie , Maladies de la volaille/immunologie , Herpèsvirus de type 1 du dindon/immunologie , Herpèsvirus de type 1 du dindon/génétique , Herpèsvirus de type 1 du dindon/métabolismeRÉSUMÉ
Marek's disease virus (MDV) vaccines were the first vaccines that protected against cancer. The avirulent turkey herpesvirus (HVT) was widely employed and protected billions of chickens from a deadly MDV infection. It is also among the most common vaccine vectors providing protection against a plethora of pathogens. HVT establishes latency in T-cells, allowing the vaccine virus to persist in the host for life. Intriguingly, the HVT genome contains telomeric repeat arrays (TMRs) at both ends; however, their role in the HVT life cycle remains elusive. We have previously shown that similar TMRs in the MDV genome facilitate its integration into host telomeres, which ensures efficient maintenance of the virus genome during latency and tumorigenesis. In this study, we investigated the role of the TMRs in HVT genome integration, latency, and reactivation in vitro and in vivo. Additionally, we examined HVT infection of feather follicles. We generated an HVT mutant lacking both TMRs (vΔTMR) that efficiently replicated in cell culture. We could demonstrate that wild type HVT integrates at the ends of chromosomes containing the telomeres in T-cells, while integration was severely impaired in the absence of the TMRs. To assess the role of TMRs in vivo, we infected one-day-old chickens with HVT or vΔTMR. vΔTMR loads were significantly reduced in the blood and hardly any virus was transported to the feather follicle epithelium where the virus is commonly shed. Strikingly, latency in the spleen and reactivation of the virus were severely impaired in the absence of the TMRs, indicating that the TMRs are crucial for the establishment of latency and reactivation of HVT. Our findings revealed that the TMRs facilitate integration of the HVT genome into host chromosomes, which ensures efficient persistence in the host, reactivation, and transport of the virus to the skin.
Sujet(s)
Poulets , Maladie de Marek , Télomère , Intégration virale , Latence virale , Animaux , Poulets/virologie , Télomère/génétique , Télomère/virologie , Maladie de Marek/virologie , Maladie de Marek/immunologie , Maladie de Marek/prévention et contrôle , Vecteurs génétiques , Herpèsvirus de type 1 du dindon/génétique , Herpèsvirus de type 1 du dindon/immunologie , Vaccins contre la maladie de Marek/immunologie , Vaccins contre la maladie de Marek/génétique , Génome viral , Herpèsvirus aviaire de type 2/génétique , Herpèsvirus aviaire de type 2/immunologie , Séquences répétées d'acides nucléiques , Maladies de la volaille/virologie , Maladies de la volaille/immunologie , Maladies de la volaille/prévention et contrôleRÉSUMÉ
The application of recombinant herpesvirus of turkey, expressing the H9 hemagglutinin gene from low pathogenic avian influenza virus (LPAIV) H9N2 and the avian orthoavulavirus-1 (AOAV-1) (commonly known as Newcastle Disease virus (NDV)) fusion protein (F) as an rHVT-H9-F vaccine, is an alternative to currently used classical vaccines. This study investigated H9- and ND-specific humoral and mucosal responses, H9-specific cell-mediated immunity, and protection conferred by the rHVT-H9-F vaccine in specific pathogen-free (SPF) chickens. Vaccination elicited systemic NDV F- and AIV H9-specific antibody response but also local antibodies in eye wash fluid and oropharyngeal swabs. The ex vivo H9-specific stimulation of splenic and pulmonary T cells in the vaccinated group demonstrated the ability of vaccination to induce systemic and local cellular responses. The clinical protection against a challenge using a LPAIV H9N2 strain of the G1 lineage isolated in Morocco in 2016 was associated with a shorter duration of shedding along with reduced viral genome load in the upper respiratory tract and reduced cloacal shedding compared to unvaccinated controls.
Sujet(s)
Anticorps antiviraux , Poulets , Sous-type H9N2 du virus de la grippe A , Vaccins antigrippaux , Grippe chez les oiseaux , Excrétion virale , Animaux , Sous-type H9N2 du virus de la grippe A/immunologie , Sous-type H9N2 du virus de la grippe A/génétique , Poulets/immunologie , Grippe chez les oiseaux/prévention et contrôle , Grippe chez les oiseaux/immunologie , Vaccins antigrippaux/immunologie , Vaccins antigrippaux/administration et posologie , Anticorps antiviraux/immunologie , Anticorps antiviraux/sang , Excrétion virale/immunologie , Organismes exempts d'organismes pathogènes spécifiques , Virus de la maladie de Newcastle/immunologie , Virus de la maladie de Newcastle/génétique , Maladies de la volaille/prévention et contrôle , Maladies de la volaille/immunologie , Maladies de la volaille/virologie , Immunité cellulaire , Herpèsvirus de type 1 du dindon/immunologie , Herpèsvirus de type 1 du dindon/génétique , Vaccination/méthodes , Immunité humorale , Vecteurs génétiques/immunologie , Immunogénicité des vaccins , Vaccins synthétiques/immunologie , Vaccins synthétiques/administration et posologie , Glycoprotéine hémagglutinine du virus influenza/immunologie , Glycoprotéine hémagglutinine du virus influenza/génétiqueRÉSUMÉ
Marek's disease virus (MDV), a causative agent of Marek's disease, has evolved its virulence partly because the current control strategies fail to provide sterilizing immunity. Gallid alphaherpesvirus 3 (GaHV-3) and turkey herpesvirus have been developed as bivalent vaccines to improve upon the level of protection elicited by single formulations. Since the in vitro passage of vaccines can result in attenuation, a GaHV-3 strain 301B/1 was cloned as a bacterial artificial chromosome (BAC) by inserting the mini-F replicon into the virus genome. A fully infectious virus, v301B-BAC, was reconstituted from the 301B/1 BAC clone and had similar growth kinetics comparable to that of the parental 301B/1 virus with strong reactivity against anti-301B/1 chicken sera. Protective efficacies of v301B-BAC, parental 301B/1, and SB-1 vaccine were evaluated against a very virulent MDV Md5 challenge. Clinical signs were significantly lower in the v301B-BAC vaccinated groups (24-25 %), parental 301B/1 (29 %) compare to that of non-vaccinated control (100%) and the removal of BAC sequences from v301B-BAC genome further reduced this to 17 %. The protective indices of v301B-BACs (75-76 %) were comparable with those of both the 301B/1 and the SB-1 vaccine (71%). Removal of the mini-F replicon resulted in a reconstituted virus with a protective index of 83 %. The shedding of challenge virus was notably lower in the v301B-BAC, and v301B-delBAC vaccinated groups. Overall, the protective efficacy of the 301B-BAC-derived vaccine virus against a very virulent MDV challenge was comparable to that of the parental 301B/1 virus as well as the SB-1 vaccine virus.
Sujet(s)
Herpèsvirus aviaire de type 2/immunologie , Maladie de Marek/immunologie , Maladies de la volaille/immunologie , Virulence/immunologie , Animaux , Poulets/virologie , Chromosomes artificiels de bactérie/génétique , Clonage moléculaire , Vecteurs génétiques/génétique , Génome viral/immunologie , Herpèsvirus de type 1 du dindon/immunologie , Maladie de Marek/virologie , Maladies de la volaille/virologie , Vaccins à ADN/génétique , Vaccins antiviraux/génétique , Réplication virale/immunologieRÉSUMÉ
Marek's disease (MD) is a complex pathology of chickens caused by MD virus (MDV) 1 and is observed as paralysis, immune suppression, neurologic signs, and the rapid formation of T-cell lymphomas. The incidence of MD in commercial broilers is largely controlled via vaccination, either in ovo or at hatch with live attenuated vaccines, i.e., turkey herpesvirus (HVT) or a bivalent combination of HVT with the MDV 2 strain (SB1). To further extend the protection conferred by bivalent HVT/SB-1, recombinant HVTs encoding transgenes of other avian viruses have similarly been used for in ovo administration. Despite decades of use, the specific mechanisms associated with vaccine-induced protection remain obscure. Additionally, the mechanistic basis for vaccine synergism conferred by bivalent HVT/SB-1, compared with HVT or SB-1 administered alone, is largely unknown. In the present study, we report on temporal changes in innate and acquired immune-patterning gene expression by using ex vivo splenocyte infection and in ovo vaccination models. We report that in the ex vivo splenocyte infection model, by 72 hr postinfection, vaccines induced IFN and IFN-stimulated gene expression, with lesser proinflammatory cytokine induction. For several genes (TLR3, IFN-γ, OASL, Mx1, NOS2A, and IL-1ß), the effects on gene expression were additive for HVT, SB1, and HVT/SB1 infection. We observed similar patterns of induction in in ovo-vaccinated commercial broiler embryos and chicks with HVT/SB-1 or recombinant HVT-based bivalent combination (HVT-LT/SB-1). Furthermore, HVT/SB-1 or HVT-LT/SB-1 in ovo vaccination appeared to hasten immune maturation, with expression patterns suggesting accelerated migration of T and natural killer cells into the spleen. Finally, HVT/SB-1 vaccination resulted in a coordinated induction of IL-12p40 and downregulation of suppressors of cytokine signaling 1 and 3, indicative of classical macrophage 1 and T-helper 1 patterning.
Análisis transcripcionales de patrones inmunes innatos y adquiridos inducidos por cepas vacunales del virus de la enfermedad de Marek: virus herpes del pavo (HVT), virus de Marek 2 (cepa SB1) y vacunas bivalentes (HVT/SB1 y HVT-LT/SB1). La enfermedad de Marek (MD) es una patología compleja de los pollos causada por el virus de Marek (MDV) 1 y se observa como parálisis, depresión inmune, signos neurológicos y la formación rápida de linfomas de células T. La incidencia de la enfermedad de Marek en pollos de engorde comerciales se controla en gran medida a través de la vacunación, ya sea in ovo o al momento de la eclosión con vacunas vivas atenuadas, por ejemplo, herpesvirus de pavo (HVT) o una combinación bivalente de HVT con la cepa SB1. Para ampliar aún más la protección conferida por la vacuna bivalente HVT/SB-1, los HVT recombinantes que codifican transgenes de otros virus aviares se han utilizado de forma similar para la administración in ovo. A pesar de décadas de uso, los mecanismos específicos asociados con la protección inducida por la vacuna siguen sin ser esclarecidos completamente. Además, el mecanismo para la sinergia de la vacuna conferida por la vacuna bivalente HVT/SB-1, en comparación con la administración de la cepa HVT o de la cepa SB-1 por sí solas, es en gran medida desconocida. En el presente estudio, se informa sobre los cambios temporales en la expresión genética de patrones inmunes innatos y adquiridos mediante la infección de esplenocitos ex vivo y en modelos de vacunación in ovo. Se reporta que en el modelo de infección de esplenocitos ex vivo, por 72 horas después de la infección, las vacunas indujeron IFN y la expresión de genes estimulada por IFN, con menor inducción de citocinas proinflamatorias. Para varios genes (TLR3, IFNc, OASL, Mx1, NOS2A e IL-1ß), los efectos sobre la expresión de genes fueron aditivos para la infección por HVT, SB1 y HVT/SB1. Se Observaron patrones de inducción similares en embriones de pollo y pollos de engorde comerciales vacunados in ovo con HVT/SB-1 o con la combinación bivalente recombinante basada en HVT (HVT-LT/SB-1). Además, la vacunación in ovo con HVT/SB-1 o HVT-LT/SB-1 parecen acelerar la maduración inmune, con patrones de expresión que sugieren una migración acelerada de células T y células asesinas naturales en el bazo. Finalmente, la vacuna HVT/SB-1 dio como resultado una inducción coordinada de IL-12p40 y una regulación a la baja de supresores de las señales de citocinas 1 y 3, indicativas de los patrones clásicos de macrófagos 1 y células cooperadoras tipo 1.
Sujet(s)
Immunité acquise/génétique , Herpèsvirus de type 1 du dindon/immunologie , Herpèsvirus aviaire de type 3/immunologie , Immunité innée/génétique , Vaccins contre la maladie de Marek/immunologie , Transcription génétique , Vaccins antiviraux/immunologie , Animaux , Embryon de poulet , Fibroblastes , Maladie de Marek/immunologieRÉSUMÉ
BACKGROUND: Marek's disease (MD) is a lymphoproliferative disease of chickens caused by Marek's disease virus (MDV), an oncogenic α-herpesvirus. Since 1970, MD has been controlled by widespread vaccination; however, more effective MD vaccines are needed to counter more virulent MDV strains. The bivalent vaccine combination of SB-1 and herpesvirus of turkey (HVT) strain FC126 has been widely used. Nonetheless, the mechanism(s) underlying this synergistic effect has not been investigated. METHODS: Three experiments were conducted where SB-1 or HVT were administered as monovalent or bivalent vaccines to newly hatched chickens, then challenged five days later with MDV. In Experiment 1, levels of MDV replication in PBMCs were measured over time, and tumor incidence and vaccinal protection determined. In Experiment 2, MDV and vaccine strains replication levels in lymphoid organs were measured at 1, 5, 10, and 14â¯days post-challenge (DPC). In Experiment 3, to verify that the bursa was necessary for HVT protection, a subset of chicks were bursectomized and these birds plus controls were similarly vaccinated and challenged, and the levels of vaccinal protection determined. RESULTS: The efficacy of bivalent SB-1â¯+â¯HVT surpasses that of either SB-1 or HVT monovalent vaccines in controlling the level of pathogenic MDV in PBMCs until the end of the study, and this correlated with the ability to inhibit tumor formation. SB-1 replication in the spleen increased from 1 to 14 DPC, while HVT replicated only in the bursa at 1 DPC. The bursa was necessary for immune protection induced by HVT vaccine. CONCLUSION: Synergy of SB-1 and HVT vaccines is due to additive influences of the individual vaccines acting at different times and target organs. And the bursa is vital for HVT to replicate and induce immune protection.
Sujet(s)
Lymphomes/médecine vétérinaire , Vaccins contre la maladie de Marek/immunologie , Maladies de la volaille/prévention et contrôle , Vaccination/médecine vétérinaire , Vaccins antiviraux/immunologie , Animaux , Poulets/immunologie , Synergie des médicaments , Herpèsvirus de type 1 du dindon/immunologie , Herpèsvirus aviaire de type 2/immunologie , Herpèsvirus aviaire de type 2/physiologie , Agranulocytes/virologie , Tissu lymphoïde/virologie , Lymphomes/prévention et contrôle , Lymphomes/virologie , Vaccins contre la maladie de Marek/administration et posologie , Cavité péritonéale/virologie , Maladies de la volaille/virologie , Vaccins antiviraux/administration et posologie , Réplication viraleRÉSUMÉ
Newcastle disease (ND) is responsible for significant economic losses in the poultry industry. The disease is caused by virulent strains of Avian avulavirus 1 (AAvV-1), a species within the family Paramyxoviridae. We developed a recombinant construct based on the herpesvirus of turkeys (HVT) as a vector expressing two genes: F and HN (HVT-NDV-F-HN) derived from the AAvV-1 genotype VI ("pigeon variant" of AAvV-1). This recombinant viral vaccine candidate was used to subcutaneously immunize one group of specific pathogen-free (SPF) chickens and two groups of broiler chickens (20 one-day-old birds/group). Humoral immune response was evaluated by hemagglutination-inhibition test and enzyme-linked immunosorbent assay (ELISA). The efficacy of the immunization was assessed in two separate challenge studies performed at 6 weeks of age with the use of virulent AAvV-1 strains representing heterologous genotypes IV and VII. The developed vaccine candidate elicited complete protection in SPF chickens since none of the birds became sick or died during the 2-week observation period. In the broiler groups, 90% and 100% clinical protection were achieved after challenges with AAvV-1 of IV and VII genotypes, respectively. We found no obvious relationship between antibody levels and protection assessed in broilers in the challenge study. The developed recombinant HVT-NDV-F-HN construct containing genes from a genotype VI AAvV-1 offers promising results as a potential vaccine candidate against ND in chickens.
Sujet(s)
Protéine HN/immunologie , Immunisation/médecine vétérinaire , Virus de la maladie de Newcastle , Vaccins synthétiques/immunologie , Protéines de fusion virale/immunologie , Animaux , Antigènes viraux/biosynthèse , Antigènes viraux/génétique , Poulets/virologie , Protection croisée , Gènes viraux , Protéine HN/biosynthèse , Protéine HN/génétique , Tests d'inhibition de l'hémagglutination , Herpèsvirus de type 1 du dindon/génétique , Herpèsvirus de type 1 du dindon/immunologie , Herpèsvirus de type 1 du dindon/métabolisme , Immunité hétérologue , Maladie de Newcastle/immunologie , Maladie de Newcastle/prévention et contrôle , Virus de la maladie de Newcastle/génétique , Virus de la maladie de Newcastle/immunologie , Maladies de la volaille/virologie , Protéines recombinantes/biosynthèse , Protéines recombinantes/génétique , Protéines recombinantes/immunologie , Vaccins synthétiques/virologie , Protéines de fusion virale/biosynthèse , Protéines de fusion virale/génétique , Vaccins antiviraux/biosynthèse , Vaccins antiviraux/immunologieRÉSUMÉ
Turkey herpesvirus (HVT) is widely used as a vaccine against Marek's disease in chickens and recently as a vector for foreign genes from infectious bursal disease virus, Newcastle disease (ND) virus, infectious laryngotracheitis (ILT) virus, and avian influenza virus. Advantages of HVT-vector vaccines are that the vaccines do not contain live respiratory viruses or live infectious bursal disease virus able to replicate and cause disease or embryo mortality, they can be administered at hatch or in ovo, and they are relatively insensitive to interference from maternally derived antibodies. As producers have tried to combine HVT-vector vaccines to protect against additional diseases, reports have indicated that applying two vectored vaccines using the same HVT vector is reported to reduce the efficacy of one or both vaccines. To confirm this interference, we evaluated commercial vaccines from multiple companies, including products with inserts designed to protect against ND, infectious ILT, and infectious bursal disease (IBD). Using a standard dosage, we found that the ILT product was most severely affected by the addition of other vaccines, as demonstrated by a significant increase in clinical signs, significant decrease in weight gain, and increase in quantity of challenge virus observed from tracheal swabs collected from Days 3-5 postchallenge. The ND and IBD products were also affected by the addition of other vaccines, although in most cases differences compared to vaccination with the vector alone were not statistically significant. This study demonstrates the importance of following manufacturer guidelines and the need for validating alternative strategies to benefit from the high level of protection offered by vector vaccines.
Evaluación de la eficacia de la protección cuando se combinan vacunas recombinantes con base en el virus herpes del pavo como vector. El virus herpes de los pavos (HVT) se usa ampliamente como una vacuna contra la enfermedad de Marek en pollos y recientemente como un vector para genes externos como del virus de la enfermedad infecciosa de la bolsa, del virus de la enfermedad de Newcastle (ND), del virus de la laringotraqueítis infecciosa (ILT) y del virus de la influenza aviar. Las ventajas de las vacunas con vector de HVT consisten en que las vacunas no contienen virus vivos respiratorios o virus de la enfermedad infecciosa de la bolsa, no son capaces de replicarse y causar enfermedad o mortalidad embrionaria, pueden administrarse en el momento de la eclosión o in ovo y son relativamente insensibles a la interferencia de anticuerpos de origen materno. A medida que los productores han intentado combinar las vacunas con el vector HVT para inducir protección contra enfermedades adicionales, los informes han indicado que la aplicación de dos vacunas vectorizadas utilizando el mismo vector HVT reduce la eficacia de una o de ambas vacunas. Para confirmar esta interferencia, se evaluaron las vacunas comerciales de múltiples compañías, incluidos los productos con inserciones diseñadas para proteger contra la enfermedad de Newcastle, la laringotraqueítis infecciosa aviar y contra la enfermedad infecciosa de la bolsa. Utilizando una dosis estándar, se encontró que el producto para la laringotraqueítis infecciosa se vio más afectado por la adición de otras vacunas, como lo demuestra un aumento significativo en los signos clínicos, una disminución significativa en el aumento de peso y un aumento en la cantidad de virus de desafío observados en los hisopos traqueales recolectados de tres a cinco días después del desafío. Los productos para la enfermedad de Newcastle y para la enfermedad de Gumboro también se vieron afectados por la adición de otras vacunas, aunque en la mayoría de los casos las diferencias en comparación con la vacunación únicamente con el vector no fueron estadísticamente significativas. Este estudio demuestra la importancia de seguir las pautas del fabricante y la necesidad de validar estrategias alternativas para beneficiarse del alto nivel de protección ofrecido por las vacunas con vectores.
Sujet(s)
Poulets , Herpèsvirus de type 1 du dindon/immunologie , Maladie de Marek/prévention et contrôle , Maladies de la volaille/prévention et contrôle , Vaccination/médecine vétérinaire , Vaccins antiviraux/immunologie , Animaux , Vecteurs génétiques , Herpèsvirus aviaire de type 1/immunologie , Virus de la bursite infectieuse/immunologie , Virus de la grippe A/immunologie , Virus de la maladie de Newcastle/immunologie , Vaccins combinés/immunologieRÉSUMÉ
Several recombinant turkey herpesviruses (rHVTs) have been developed within the past decades, and they are now used commercially worldwide. In broiler chickens, rHVTs are usually administered alone, but in long-living birds they are used in combination with Marek's disease (MD) vaccines of other serotypes (i.e., CVI988). The objectives of this work were to 1) evaluate protection against MD conferred by HVT and two rHVTs when combined with CVI988 and 2) optimize the use of rHVT in combination with CVI988 to maximize replication of rHVT without compromising MD protection. Various vaccine protocols, all using rHVT or HVT at the recommended dose (RD), were evaluated. Protocols evaluated included in ovo vaccination with HVT+CVI988 or rHVT+CVI988 (using either the double dose [DD] or the RD of CVI988), day of age vaccination of rHVT+CVI988 at DD, and revaccination protocols using rHVT in ovo followed by CVI988 at DD at day of age. Our results show that, when combined with CVI988, HVT and rHVTs confer a similar level of protection against MD (>90%) regardless of whether CVI988 was used at RD or at DD. However, the combination of rHVT with CVI988 at DD resulted in reduced replication rates of rHVT (60%-76% vs. 95%-100%). Our results show that such a negative effect could be avoided without jeopardizing MD protection by administering CVI988 at RD (if combined in ovo with rHVT) or administered rHVT first in ovo followed by CVI988 at DD at day of age.
Estudio de la eficacia y replicación de vacunas con vectores recombinantes mediante el uso del virus del herpes del pavo combinado con otras vacunas contra la enfermedad de Marek. Varios herpesvirus de pavo recombinantes (rHVT) se han desarrollado en las últimas décadas y ahora se utilizan comercialmente en todo el mundo. En pollos de engorde, los rHVT generalmente se administran solos, pero en aves de vida larga se usan en combinación con vacunas contra la enfermedad de Marek (MD) de otros serotipos (especialmente, CVI988). Los objetivos de este trabajo fueron 1) evaluar la protección contra la enfermedad de Marek conferida por herpesvirus de pavo (HVT9 y por dos rHVT cuando se combinan con la cepa CVI988 y 2) optimizar el uso de rHVT en combinación con la cepa CVI988 para maximizar la replicación de rHVT sin comprometer la protección contra la enfermedad de Marek. Se evaluaron varios protocolos de vacunas, todos con rHVT o con HVT a la dosis recomendada (RD). Los protocolos evaluados incluyeron la vacunación in ovo con HVT + CVI988 o rHVT + CVI988 (usando la dosis doble o la dosis recomendada de la cepa CVI988), la vacunación al día de la edad con rHVT + CVI988 con dosis doble, y los protocolos de revacunación usando rHVT seguido por la cepa CVI988 con dosis doble al día de edad. Los resultados muestran que cuando se combinan con CVI988, HVT y rHVT confieren un nivel de protección similar contra la enfermedad de Marek (> 90%) independientemente de que la cepa CVI988 se haya usado a la dosis recomendada o con dosis doble. Sin embargo, la combinación de rHVT con la cepa CVI988 con doble dosis produjo una reducción en las tasas de replicación de rHVT (60% 76% vs. 95% 100%). Estos resultados muestran que dicho efecto negativo podría evitarse sin poner en peligro la protección contra la enfermedad de Marek administrando la cepa CVI988 a la dosis recomendada (si se combina in ovo con rHVT) o administrando rHVT primero in ovo, seguido de CVI988 con dosis doble al día de la edad.
Sujet(s)
Poulets , Herpèsvirus de type 1 du dindon/immunologie , Herpèsvirus aviaire de type 2/immunologie , Vaccins contre la maladie de Marek/pharmacologie , Maladie de Marek/prévention et contrôle , Maladies de la volaille/prévention et contrôle , Animaux , Femelle , Maladie de Marek/virologie , Maladies de la volaille/virologie , Vaccination/médecine vétérinaireRÉSUMÉ
Marek's Disease is a lymphoproliferative disease of chickens caused by Marek's Disease Virus. Similar to other herpesviruses, Marek's Disease Virus (MDV) encodes its own small non-coding regulatory RNAs termed microRNAs (miRNAs). We previously found that the expression profile of these viral miRNAs is affected by vaccination with Herpesvirus of Turkeys (HVT). To further characterize miRNA-mediated gene regulation in MDV infections, in the current study we examine the impact of HVT vaccination on cellular miRNA expression in MDV-infected specific-pathogen-free (SPF) chickens. We used small RNA-seq to identify 24 cellular miRNAs that exhibited altered splenic expression in MDV infected chickens (42 dpi) compared to age-matched uninfected birds. We then used Real Time-quantitative PCR (RT-qPCR) to develop expression profiles of a select group of these host miRNAs in chickens receiving the HVT vaccine and in vaccinated chickens subsequently infected with MDV. As was seen with viral miRNA, host miRNAs had unique splenic expression profiles between chickens infected with HVT, MDV, or co-infected birds. We also discovered a group of transcription factors, using a yeast one-hybrid screen, which regulates immune responses and cell growth pathways and also likely regulates the expression of these cellular miRNAs. Overall, this study suggests cellular miRNAs are likely a critical component of both protection from and progression of Marek's Disease.
Sujet(s)
Maladie de Marek/génétique , microARN/génétique , Rate/métabolisme , Vaccination/médecine vétérinaire , Animaux , Embryon de poulet , Herpèsvirus de type 1 du dindon/immunologie , Herpèsvirus de type 1 du dindon/pathogénicité , Maladie de Marek/immunologie , Maladie de Marek/prévention et contrôle , Maladie de Marek/virologie , microARN/métabolismeRÉSUMÉ
A double recombinant strain of herpes virus of turkeys (HVT) was constructed that contains the fusion (F) gene from Newcastle disease virus (NDV) and the gD plus gI genes from infectious laryngotracheitis virus (ILTV) inserted into a non-essential region of the HVT genome. Expression of the F protein was controlled by a human cytomegalovirus promoter, whereas expression of gD plus gI was driven by an ILTV promoter. The double recombinant vaccine virus (HVT-NDV-ILT) was fully stable genetically and phenotypically following extended passage in cell culture and infection of chickens. Safety of the vaccine virus was confirmed by overdose and backpassage studies in specific-pathogen-free chickens. Chickens vaccinated with a single dose of HVT-NDV-ILT administered by the in ovo route were highly protected from challenge with the velogenic NDV (GB Texas), ILTV (LT 96-3) and Marek's disease virus (GA 5) strains (97%, 94% and 97%, respectively). Similarly, chickens vaccinated with a single dose by subcutaneous (SC) route at 1 day of age were highly protected from challenge with the same three viruses (100%, 100%, and 88%, respectively). The protection level of a single dose given by in ovo or SC route against challenge with a virulent Marek's disease virus strain demonstrates that insertion of multiple genes from two different pathogens within the HVT genome had no adverse effect on the capacity of HVT to protect against Marek's disease. These results demonstrate that HVT-NDV-ILT is a safe and efficacious vaccine for simultaneous control of NDV, ILTV and Marek's diseases.
Sujet(s)
Poulets/virologie , Herpèsvirus aviaire de type 1/immunologie , Herpèsvirus de type 1 du dindon/immunologie , Herpèsvirus aviaire de type 2/immunologie , Maladie de Marek/prévention et contrôle , Maladies de la volaille/prévention et contrôle , Animaux , Maladie de Marek/virologie , Maladies de la volaille/virologie , Organismes exempts d'organismes pathogènes spécifiques , DindonsRÉSUMÉ
The outbreak of highly pathogenic avian influenza virus in North American poultry during 2014 and 2015 demonstrated the devastating effects of the disease and highlighted the need for effective emergency vaccine prevention and control strategies targeted at currently circulating strains. This study evaluated the efficacy of experimental recombinant turkey herpesvirus vector vaccines with three different inserts targeting the hemagglutinin gene of an isolate from the recent North American influenza outbreak. White leghorn chickens were vaccinated at one day of age and challenged with A/Turkey/Minnesota/12582/2015 H5N2 at 4â¯weeks of age. Birds were analyzed for survival, viral shedding at two and four days after infection, and specific antibody prior to challenge and from surviving birds. The three experimental vaccines demonstrated 100%, 45% and 15% survival with the most effective vaccine significantly reducing oral and cloacal viral shedding compared to all other groups and generated specific antibody prior to challenge with highly pathogenic avian influenza virus. More studies are needed using diverse H5Nx highly pathogenic virus isolates to fully determine the breadth of coverage against possible exposure strains, as well as possible impact of maternally derived antibody on protection and vaccine efficacy.
Sujet(s)
Glycoprotéine hémagglutinine du virus influenza/immunologie , Herpèsvirus de type 1 du dindon/immunologie , Vaccins contre les herpèsvirus/génétique , Sous-type H5N2 du virus de la grippe A/immunologie , Vaccins antigrippaux/immunologie , Grippe chez les oiseaux/prévention et contrôle , Animaux , Anticorps antiviraux/sang , Poulets , Épidémies de maladies/prévention et contrôle , Vecteurs génétiques/administration et posologie , Vecteurs génétiques/immunologie , Glycoprotéine hémagglutinine du virus influenza/administration et posologie , Glycoprotéine hémagglutinine du virus influenza/génétique , Herpèsvirus de type 1 du dindon/génétique , Vaccins contre les herpèsvirus/administration et posologie , Sous-type H5N2 du virus de la grippe A/génétique , Sous-type H5N2 du virus de la grippe A/isolement et purification , Sous-type H5N2 du virus de la grippe A/pathogénicité , Vaccins antigrippaux/administration et posologie , Vaccins antigrippaux/génétique , Grippe chez les oiseaux/épidémiologie , Grippe chez les oiseaux/immunologie , Maladies de la volaille/prévention et contrôle , Maladies de la volaille/virologie , États-Unis/épidémiologie , Vaccination , Efficacité du vaccin , Vaccins synthétiques/administration et posologie , Vaccins synthétiques/génétique , Vaccins synthétiques/immunologie , Excrétion viraleRÉSUMÉ
Newcastle disease (ND) is still a major poultry disease worldwide. Vaccination remains the principal method of controlling ND in endemic countries. Various vaccination strategies, including the use of recently developed recombinant vaccines, have been used to control it. Recombinant vaccines that use the herpesvirus of turkey (HVT) as a vector to express one of the key antigens of Newcastle disease virus (NDV) have been developed to overcome some of the drawbacks related to the use of conventional vaccines. HVT as a vector appears to have unique beneficial characteristics: it is extremely safe, it is not affected by the presence of maternally derived antibodies, and therefore can be applied in the hatchery either in ovo or to day-old chicks. Due to its persistence in the bird, the HVT vector can be expected to induce life-long immune stimulation. In the present study, the efficacy of an HVT-based vector vaccine expressing the F gene of NDV (rHVT-F) was tested against a velogenic genotype IV NDV challenge in commercial turkeys with high levels of maternal antibodies (8.7 ± 0.8 log2 hemagglutination inhibition titer). The birds were vaccinated on the day of hatch by the subcutaneous route. Development of a humoral immune response to vaccination was detectable from 4 weeks of age by ELISA. The challenge strain used represents recent NDV genotype IV field strains from Morocco. Challenge with this strain induced ND-specific clinical signs and stunting without subsequent mortality in the non-vaccinated birds, whereas the vaccinated turkey poults showed protection as early as 3 weeks of age based on lack of clinical signs, better body weight gain, and reduction of challenge virus shedding. This is the first reported efficacy study of an HVT-vectored ND vaccine against a velogenic NDV challenge in commercial turkeys.
Sujet(s)
Herpèsvirus de type 1 du dindon/immunologie , Immunité innée , Maladie de Newcastle/prévention et contrôle , Virus de la maladie de Newcastle/immunologie , Maladies de la volaille/prévention et contrôle , Vaccins antiviraux/immunologie , Animaux , Maladie de Newcastle/virologie , Maladies de la volaille/virologie , Dindons , Vaccins synthétiques/immunologieRÉSUMÉ
Chickens are commonly processed around 35-45days of age in broiler chicken industry hence; diseases that occur at a young age are of paramount economic importance. Early age infection with infectious bursal disease virus (IBDV) results in long-lasting immunosuppression and profound economic losses. To our knowledge, this is the first study comparing the protection efficacy of modified live (MdLV) IBDV and herpesvirus turkey (HVT)-IBDV vaccines against early age variant IBDV (varIBDV) infection in chicks. Experiments were carried out in IBDV maternal antibody (MtAb) positive chicks (n=330), divided into 6 groups (n=50-60/group), namely Group 1 (saline), Group 2 (saline+varIBDV), Group 3 (HVT-IBDV), Group 4 (HVT-IBDV+varIBDV), Group 5 (MdLV) and Group 6 (MdLV+varIBDV). HVT-IBDV vaccination was given via the in ovo route to 18-day-old embryonated eggs. MdLV was administered via the subcutaneous route in day-old broilers. Group 2, Group 4 and Group 6 were orally challenged with varIBDV (SK-09, 3×103 EID50) at day 6 post-hatch. IBDV seroconversion, bursal weight to body weight ratio (BBW) and bursal histopathology were assessed at 19 and 35days of age. Histopathological examination at day 19 revealed that varIBDV-SK09 challenge caused severe bursal atrophy and lower BBW in HVT-IBDV but not in MdLV vaccinated chicks. However by day 35, all challenged groups showed bursal atrophy and seroconversion. Interestingly, RT-qPCR analysis after varIBDV-SK09 challenge demonstrated an early (9days of age) and significantly high viral load (â¼5744 folds) in HVT-IBDV vaccinated group vs unvaccinated challenged group (â¼2.25 folds). Furthermore, flow cytometry analysis revealed inhibition of cytotoxic CD8+ T-cell response (CD44-downregulation) and decreased splenic lymphocytes counts in chicks after HVT-IBDV vaccination. Overall, our data suggest that MdLV delays varIBDV pathogenesis, whereas, HVT-IBDV vaccine is potentially immunosuppressive, which may increase the risk of early age varIBDV infection in broilers.
Sujet(s)
Infections à Birnaviridae/prévention et contrôle , Poulets/virologie , Maladie de Marek/prévention et contrôle , Maladies de la volaille/prévention et contrôle , Vaccination , Vaccins antiviraux/administration et posologie , Animaux , Animaux nouveau-nés , Anticorps antiviraux/biosynthèse , Infections à Birnaviridae/immunologie , Infections à Birnaviridae/anatomopathologie , Infections à Birnaviridae/virologie , Bourse de Fabricius/effets des médicaments et des substances chimiques , Bourse de Fabricius/immunologie , Bourse de Fabricius/anatomopathologie , Bourse de Fabricius/virologie , Embryon de poulet , Poulets/immunologie , Herpèsvirus de type 1 du dindon/effets des médicaments et des substances chimiques , Herpèsvirus de type 1 du dindon/immunologie , Herpèsvirus de type 1 du dindon/pathogénicité , Virus de la bursite infectieuse/effets des médicaments et des substances chimiques , Virus de la bursite infectieuse/immunologie , Virus de la bursite infectieuse/pathogénicité , Maladie de Marek/immunologie , Maladie de Marek/anatomopathologie , Maladie de Marek/virologie , Taille d'organe/effets des médicaments et des substances chimiques , Maladies de la volaille/immunologie , Maladies de la volaille/anatomopathologie , Maladies de la volaille/virologie , Lymphocytes T cytotoxiques/effets des médicaments et des substances chimiques , Lymphocytes T cytotoxiques/immunologie , Lymphocytes T cytotoxiques/virologie , Facteurs temps , Vaccins vivants non atténués , Zygote/effets des médicaments et des substances chimiquesRÉSUMÉ
We constructed turkey herpesvirus (HVT) vector vaccines in which the VP2 gene of infectious bursal disease virus (IBDV) was inserted into the HVT genome in the following regions: UL3-4, UL22-23, UL45-46, and US10-SORF3. We then evaluated the relationship between the gene insertion site and the capacity of the virus to elicit antibodies. rHVT/IBD (US10) showed good growth activity in vitro, with growth comparable to that of the parent HVT. On the other hand, rHVT/IBD (UL3-4), rHVT/IBD (UL22-23), and rHVT/IBD (UL45-46) exhibited decreased growth activity in chicken embryo fibroblast (CEF) cells compared to the parent HVT. However, the rHVT/IBD (US10) elicited lower levels of virus-neutralizing (VN) antibodies compared to the other constructs. rHVT/IBD (UL3-4) and rHVT/IBD (UL45-46) appeared to be similar in their ability to elicit VN antibodies. Based on the results of in vitro and in vivo assays, rHVT/IBD (UL3-4) was selected for further testing. In a challenge assay, rHVT/IBD (UL3-4) protected chickens from challenge with virulent Marek's disease virus serotype 1 and IBDV. In conclusion, the site of gene insertion may have a strong effect on the growth of the vector virus in vitro and its antibody-eliciting capacity. Insertions in the UL3-4 region permitted a balance between growth activity and VN-antibody-eliciting capacity, and this region might therefore be an appropriate insertion site for IBDV VP2.
Sujet(s)
Anticorps antiviraux/immunologie , Herpèsvirus de type 1 du dindon/immunologie , Maladie de Marek/prévention et contrôle , Maladies de la volaille/prévention et contrôle , Protéines virales/immunologie , Vaccins antiviraux/immunologie , Animaux , Poulets , Herpèsvirus de type 1 du dindon/composition chimique , Herpèsvirus de type 1 du dindon/génétique , Herpèsvirus de type 1 du dindon/croissance et développement , Herpèsvirus aviaire de type 2/immunologie , Herpèsvirus aviaire de type 2/physiologie , Maladie de Marek/immunologie , Maladie de Marek/virologie , Mutagenèse par insertion , Maladies de la volaille/immunologie , Maladies de la volaille/virologie , Dindons , Vaccination , Vaccins synthétiques/administration et posologie , Vaccins synthétiques/composition chimique , Vaccins synthétiques/génétique , Vaccins synthétiques/immunologie , Protéines virales/administration et posologie , Protéines virales/composition chimique , Protéines virales/génétique , Vaccins antiviraux/administration et posologie , Vaccins antiviraux/composition chimique , Vaccins antiviraux/génétiqueRÉSUMÉ
Infectious bursal disease (IBD) is an avian viral disease that causes severe economic losses in the poultry industry worldwide. The live IBD virus (IBDV) has a potential immunosuppressive effect. Currently available IBDV vaccines have shortcomings, prompting the development of safer and more effective vaccination approaches, including the use of the recombinant turkey herpesvirus vaccine expressing the immunogenic structural VP2 protein of IBDV (recombinant HVT (rHVT)-IBD). The objectives of this study were twofold: (i) to develop in vitro assays and molecular tools to detect the VP2 protein and gene and (ii) to evaluate cell-mediated immunity (CMI) induced by rHVT-IBD vaccination of day-old specific pathogen-free chickens. The VP2 protein expressed by rHVT-IBD-infected chicken embryo fibroblasts was detected using the enzyme-linked immunosorbent assay and immunofluorescence. Using molecular techniques, the VP2 gene was detected in various organs, providing a method to monitor vaccine uptake. rHVT-IBD vaccination induced CMI responses in specific pathogen-free chickens at 5 weeks. CMI was detected by measuring chicken interferon-gamma after ex vivo antigenic stimulation of splenocytes. Moreover, our results showed that the enzyme-linked immunospot approach is more sensitive in detecting chicken interferon-gamma than enzyme-linked immunosorbent assay. The tools developed in this study may be useful in the characterization of new-generation recombinant vaccines and the cellular immune response they induce.
Sujet(s)
Anticorps antiviraux/immunologie , Infections à Birnaviridae/médecine vétérinaire , Herpèsvirus de type 1 du dindon/immunologie , Virus de la bursite infectieuse/immunologie , Maladies de la volaille/prévention et contrôle , Vaccins antiviraux/immunologie , Animaux , Infections à Birnaviridae/prévention et contrôle , Infections à Birnaviridae/virologie , Poulets , Test ELISA/médecine vétérinaire , Immunité cellulaire , Interféron gamma/immunologie , Mâle , Maladies de la volaille/virologie , Organismes exempts d'organismes pathogènes spécifiques , Vaccination/médecine vétérinaire , Vaccins synthétiques/immunologie , Protéines virales structurales/génétique , Protéines virales structurales/immunologieRÉSUMÉ
Infectious bursal disease (IBD) is a major disease affecting the poultry industry and is caused by infection with IBD virus (IBDV). To develop a novel vaccine to prevent IBD in chickens, recombinant Marek's disease virus Rispens viruses carrying the VP2 gene of IBDV driven by five different promoters (Rispens/IBD) were constructed using homologous recombination and a bacterial artificial chromosome (BAC). Rispens/IBD driven by the chicken beta-actin (Bac) promoter (Rispens/Bac-IBD), Rous sarcoma virus promoter, or simian virus 40 promoter were administered to 1-day-old SPF chicks, and the protective efficacy against IBDV was evaluated by challenging chicks with virulent IBDV. As a result, Rispens/Bac-IBD showed the best protection (87%). Next, we constructed the virus driven by the Bac-derived Coa5 promoter (Rispens/Coa5-IBD) for a secondary in vivo trial using commercial layer chickens since Rispens/Bac-IBD was thought to be genetically unstable. Rispens/Coa5-IBD showed stability in vitro and exhibited better antibody production and protection during challenge against virulent IBDV at both 5 (95%) and 7 wk of age (91%) compared with that of Rispens/Bac-IBD (90% at 5 wk of age and 84% at 7 wk of age). Thus, Rispens/Coa5-IBD may be a novel promising vaccine against IBD and virulent Marek's disease.
Sujet(s)
Infections à Birnaviridae/médecine vétérinaire , Poulets , Virus de la bursite infectieuse/immunologie , Maladies de la volaille/prévention et contrôle , Vaccins antiviraux/immunologie , Animaux , Infections à Birnaviridae/prévention et contrôle , Herpèsvirus de type 1 du dindon/immunologie , Maladie de Marek/prévention et contrôle , Vaccins contre la maladie de Marek/immunologie , VirulenceRÉSUMÉ
Herpesvirus of turkeys (HVT) has been successfully used as a Marek's disease (MD) vaccine for more than 40 yr. Either alone (broiler chickens) or in combination with vaccines of other serotypes (broilers, broiler breeders, and layers), HVT is used worldwide. In recent years, several vector vaccines based on HVT (rHVT) have been developed. At present, there are both conventional HVT and rHVTs in the market, and it is unknown if all of them confer the same level of protection against MD. The objective of this study was to further characterize the protection conferred by two conventional HVTs (HVT-A and HVT-B) and three recombinant HVTs (rHVT-B, rHVT-C, and rHVT-D) against MD in broiler chickens. In a first study we evaluated the efficacy of two conventional HVTs (HVT-A and HVT-B) administered at different doses (475, 1500, and 4000 PFU) at day of age on the ability to protect against an early challenge with very virulent plus strain 645. In a second experiment we evaluated the protection ability of several HVTs (both conventional and recombinant) when administered in ovo at a dose of 1500 PFU using the same challenge model. Our results show that each HVT product is unique, regardless of being conventional or recombinant, in their ability to protect against MD and might require different PFUs to achieve its maximum efficacy. In Experiment 1, HVT-A at 4000 PFU conferred higher protection (protection index [PI] = 63) than any of the other vaccine protocols (PI ranging from 36 to 47). In Experiment 2, significant differences were found among vaccine protocols with PI varying from 66 (HVT-A) to 15 (rHVT-D). Our results show that each HVT is unique and age at vaccination and vaccine dose greatly affected vaccine efficacy. Furthermore, they highlight the need of following manufacturer's recommendations.