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.
CVI-LTR replicates in the thymus and spleen earlier than CVI988.CVI-LTR replicates in lymphoid organs but it cannot be detected in feather pulp.CVI-LTR reduced the load of oncogenic MDV DNA more efficiently than CVI988.
Marek's disease virus (MDV) is a herpesvirus that induces lymphoma and immunosuppression in chickens. MDV-induced immunosuppression (MDV-IS) is complex and can be divided into two phases: early-MDV-IS associated with cytolytic infection in the lymphoid organs in chickens lacking maternal antibodies against MDV (MAbs) and late-MDV-IS that appears later in the pathogenesis and occurs even in chickens bearing MAbs. We have recently developed a model to reproduce late-MDV-IS under laboratory conditions. This model evaluates late-MDV-IS indirectly by assessing the effect of MDV infection on the efficacy of infectious laryngotracheitis (ILT) vaccines against challenge with ILT virus. In the present study, we have used this model to investigate the role of two factors (MDV pathotype and host sex) on the development of late-MDV-IS. Five MDV strains representing three different pathotypes: virulent (vMDV; 617A, GA), very virulent (vvMDV; Md5), and very virulent plus (vv+MDV; 648A, 686), were evaluated. Only vv+ strains were able to induce late-MDV-IS. An immunosuppression rank (IS-rank) was established based on the ability of MDV to reduce the efficacy of chicken embryo origin vaccine (values go from 0 to 100, with 100 being the highest immunosuppressive ability). The IS-rank of the evaluated MDV strains ranged from 5.97 (GA) to 20.8 (617A) in the vMDV strains, 5.97 to 16.24 in the vvMDV strain Md5, and 39.08 to 68.2 in the vv+ strains 648A and 686. In this study both male and female chickens were equally susceptible to MDV-IS by vv+MDV 686. Our findings suggest that late-MDV-IS is a unique feature of vv+ strains.
Marek's disease virus (MDV) is a herpesvirus that induces lymphomas and immunosuppression in chickens. MDV-induced immunosuppression (MDV-IS) is divided into two phases: early-MDV-IS occurring mainly in chickens lacking maternal antibodies (MAb) against MDV and associated with lymphoid organ atrophy; and late-MDV-IS occurring once MDV enters latency and during tumour development. Our objectives were to document the impact of late-MDV-IS on commercial poultry (meat-type chickens bearing MAb against MDV and that were vaccinated or unvaccinated against MD) and to optimize a model to study late-MDV-IS under laboratory conditions. The impact of late-MDV-IS was evaluated by assessing the effect of early infection (day of age) with a very virulent plus MDV (vv+MDV) on the efficacy of chicken-embryo-origin (CEO) infectious laryngotracheitis (ILT) virus vaccine against ILT challenge. The CEO ILT vaccine was administered in water at 14 days of age and ILT virus (ILTV) challenge was done intratracheally at 30 days of age. Development of ILT was monitored by daily evaluation of clinical signs, development of gross and histological lesions in trachea, and quantification of ILTV transcripts in trachea. Infection with vv+MDV strain 648A resulted in total abrogation of protection conferred by the CEO vaccine against ILTV challenge even in chickens vaccinated at 1 day of age with either HVT, HVT+SB-1, or CVI988. Chickens exposed to vv+MDV prior to vaccination with CEO ILTV vaccine had similar (P
Marek's disease virus (MDV) is a herpesvirus that induces lymphoma and a variety of non-neoplastic syndromes in chickens. Furthermore, very virulent plus (vv+) MDVs induce a form of immunosuppression (late-MDV-IS) that might involve both neoplastic and non-neoplastic mechanisms. The objective of this study was to evaluate whether the attenuation of MDV-induced tumours and late-MDV-IS occurs simultaneously or can be dissociated. The immunosuppressive ability of three viruses derived from vv+ MDV strain 686 (wild-type 686, the somewhat attenuated molecular clone 686-BAC, and the nononcogenic molecular clone lacking the two copies of the oncogene meq 686-BACΔMEQ) was evaluated. Late-MDV-IS was evaluated indirectly by assessing the negative effect of MDV strains on the protection conferred by infectious laryngotracheitis (ILT) vaccines. Our results showed that the ability to induce late-MDV-IS was attenuated before the ability to induce tumours. Strain 686 induced both tumours and late-MDV-IS, 686-BAC induced tumours but did not induce late-MDV-IS and 686-BACΔMEQ did not induce either tumours or late-MDV-IS. Further comparison of strains 686 and 686-BAC revealed that strain 686 reduced the humoral immune responses to ILTV (1132 vs 2167) more severely, showed higher levels of meq transcripts (2.1E+09 vs 4.98E+8) and higher expression of MDV microRNAs (mdv1-miR-M4-5p and mdv1-miR-M2-3p) in the spleen, and further reduced the percentage of CD45+-MHC-I+splenocytes (13 vs32 %) compared to molecular clone 686-BAC. This study suggests that the immunosuppressive ability of MDV might follow a continuous spectrum and only the most virulent MDVs can overcome a certain threshold level and induce clinical MDV-IS in the ILT model.
Md5-BAC-REV-LTR is a recombinant Marek's disease virus (MDV), with an insertion of the long terminal repeat (LTR) of reticuloendotheliosis virus (REV) into the genome of the highly virulent MDV strain rMd5. It has been shown that Md5-BAC-REV-LTR does not induce tumours and confers high protection against challenge with MDV in 15 × 7 chickens. The objective of the present study was to evaluate the protection and safety (in terms of oncogenicity and immunosuppression) of Md5-BAC-REV-LTR in commercial meat-type chickens bearing maternal antibodies against MDV. Our results show that sub-cutaneous administration of Md5-BAC-REV-LTR at 1 day of age conferred high protection (protection index PI = 84.2) against an early challenge (1 day) by contact exposure to shedder birds infected with the vv+ MDV 648A strain. In such stringent challenge conditions, Md5-BAC-REV-LTR was more protective than a commercial CVI988 (PI = 12.4) and similar to the experimental vaccine Md5-BACΔmeq (PI = 92.4). Furthermore, Md5-BAC-REV-LTR did not induce either tumours or immunosuppression in this study. Immunosuppression was evaluated by the relative lymphoid organ weights and also by the ability of the vaccine to induce late-MDV-induced immunosuppression associated with reactivation of the virus. This study shows that Md5-BAC-REV-LTR has the potential to be used as a MD vaccine and is highly protective against early challenge with vv+ MDV.RESEARCH HIGHLIGHTSMd5-BAC-REV-LTR is highly protective against early challenge with vv+ MDV in commercial meat-type chickens.Md5-BAC-REV-LTR does not cause early immunosuppression.Md5-BAC-REV-LTR does not cause late immunosuppression.Unlike other serotype 1 vaccines, Md5-BAC-REV-LTR is not detected in feather pulp at 7 days post vaccination.
Understanding the pathogenesis of herpesvirus of turkeys (HVT) in its natural host is necessary before recombinant HVT (rHVT) can be used efficiently in turkey flocks. The objectives of this study were to evaluate when commercial turkey flocks get infected with wild type HVT, to study replication of HVT (conventional and recombinant rHVT-Newcastle disease, rHVT-ND) and other Marek's disease (MD) vaccines (SB-1 and CVI988) in turkey embryonic tissues, and to evaluate the expression of TLR-3 and IFN-γ in the lung and spleen of one-day-old turkeys after in ovo vaccination with MD vaccines. Our results demonstrated that commercial turkeys got exposed to wild type HVT within the first days of life; therefore, there is a potential of interaction between wild type HVT and rHVT when administered at day of age. On the other hand, all evaluated vaccines (especially HVT and rHVT-ND) replicated very well in turkey embryonic tissues. In ovo vaccination with HVT and CVI988 increased transcription of TLR-3 in the spleen of one-day-old turkeys. However, no effect on the transcription of TLR-3 or IFN-γ in the lungs and IFN-γ in the spleen in newly hatched turkeys was detected in the present study. Because of the limitations of evaluated genes, timepoints, and studied tissues, future studies are warranted to better understand the effect of MD vaccines on the turkey embryo immune responses.RESEARCH HIGHLIGHTS Commercial turkey flocks get infected with wild type HVT within the first days of life.HVT and rHVT replicates readily in turkey embryonic tissues.SB-1 and CVI988 also replicate in turkey embryonic tissues, but at lower rates than HVT and rHVT.HVT and CVI988 increase transcription of TLR-3 in the spleen.