Dataset Information

Development of a Recombinant Pichinde Virus-Vectored Vaccine against Turkey Arthritis Reovirus and Its Immunological Response Characterization in Vaccinated Animals.

ABSTRACT: Vaccination may be an effective way to reduce turkey arthritis reovirus (TARV)-induced lameness in turkey flocks. However, there are currently no commercial vaccines available against TARV infection. Here, we describe the use of reverse genetics technology to generate a recombinant Pichinde virus (PICV) that expresses the Sigma C and/or Sigma B proteins of TARV as antigens. Nine recombinant PICV-based TARV vaccines were developed carrying the wild-type S1 (Sigma C) and/or S3 (Sigma B) genes from three different TARV strains. In addition, three recombinant PICV-based TARV vaccines were produced carrying codon-optimized S1 and/or S3 genes of a TARV strain. The S1 and S3 genes and antigens were found to be expressed in virus-infected cells via reverse transcriptase polymerase chain reaction (RT-PCR) and the direct fluorescent antibody (DFA) technique, respectively. Turkey poults inoculated with the recombinant PICV-based TARV vaccine expressing the bivalent TARV S1 and S3 antigens developed high anti-TARV antibody titers, indicating the immunogenicity (and safety) of this vaccine. Future in vivo challenge studies using a turkey reovirus infection model will determine the optimum dose and protective efficacy of this recombinant virus-vectored candidate vaccine.

SUBMITTER: Kumar P

PROVIDER: S-EPMC7918942 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Development of a Recombinant Pichinde Virus-Vectored Vaccine against Turkey Arthritis Reovirus and Its Immunological Response Characterization in Vaccinated Animals.

Kumar Pawan P Sharafeldin Tamer A TA Kumar Rahul R Huang Qinfeng Q Liang Yuying Y Goyal Sagar M SM Porter Robert E RE Ly Hinh H Mor Sunil K SK

Pathogens (Basel, Switzerland) 20210213 2

Vaccination may be an effective way to reduce turkey arthritis reovirus (TARV)-induced lameness in turkey flocks. However, there are currently no commercial vaccines available against TARV infection. Here, we describe the use of reverse genetics technology to generate a recombinant Pichinde virus (PICV) that expresses the Sigma C and/or Sigma B proteins of TARV as antigens. Nine recombinant PICV-based TARV vaccines were developed carrying the wild-type S1 (Sigma C) and/or S3 (Sigma B) genes from ...[more]

PMID: 33668435

Similar Datasets

Project description:BackgroundTurkey arthritis reovirus (TARV) causes arthritic lameness in market-age turkeys. Since 2011, highly pathogenic TARV strains have caused significant economic losses in the turkey industry due to increased culling, reduced market weights, and decreased carcass quality, necessitating more effective control measures. Autogenous vaccine prevention strategies have been inefficacious partly due to a limited understanding of age-related susceptibility of turkeys to TARV. This study investigated age-related host and gut microbiota responses to TARV infection in commercial turkeys derived from vaccinated breeder hens. Poults with known maternally derived antibody titers were orally challenged with TARV O'Neil strain at 1-, 3-, and 7- weeks of age (WOA) and monitored for cloacal virus shedding, gastrocnemius tendon viral tropism, tendon inflammation, weight gain, and changes in gut microbiota.ResultsA transient TARV-induced weight gain suppression was evident in poults infected at 1- and 3- WOA during the first 3 weeks post-infection. Age-dependent variations in cloacal viral shedding, virus isolation from tendons, and tendon inflammation severity were also observed. There was significant dissimilarity in ileal and cecal bacterial communities between mock and infected groups, but the effect of age of infection was unclear.ConclusionsAge dependent host response was observed to TARV based on cloacal virus shedding, weight gain suppression and viral tendon tropism. Our study also indicates that maternally derived antibodies appeared insufficient to prevent virus translocation to the tendons and subsequent pathological changes. This study lays the groundwork for future investigations of better vaccines/vaccination strategies and alternative preventive measures.ImportanceTurkey arthritis reovirus (TARV) causes lameness due to arthritis and tenosynovitis, commonly in market-age turkeys, resulting in significant economic losses. As a control strategy, the turkey industry used autogenous vaccines, prepared from field TARV isolates in breeder hens, to protect the poults in the early stage of life through maternally derived antibodies (MDAs). This study establishes the level of protection provided by MDAs in young poults with age-based responses to TARV O'Neil reovirus strain. Additionally, this study reveals the dynamics of gut dysbiosis in infected poults at different timepoints, paving the way to ground-breaking investigations into gut microbiome modulation interventions that could potentially improve vaccine efficacy and reduce virus transmission and disease severity.

Project description:Mammarenaviruses include several highly virulent pathogens (e.g., Lassa virus) capable of causing severe hemorrhagic fever diseases for which there are no approved vaccines and limited treatment options. Mammarenaviruses are enveloped, bi-segmented ambisense RNA viruses. There is limited knowledge about cellular proteins incorporated into progeny virion particles and their potential biological roles in viral infection. Pichinde virus (PICV) is a prototypic arenavirus used to characterize mammarenavirus replication and pathogenesis. We have developed a recombinant PICV with a tri-segmented RNA genome as a viral vector platform. Whether the tri-segmented virion differs from the wild-type bi-segmented one in viral particle morphology and protein composition has not been addressed. In this study, recombinant PICV (rPICV) virions with a bi-segmented (rP18bi) and a tri-segmented (rP18tri) genome were purified by density-gradient ultracentrifugation and analyzed by cryo-electron microscopy and mass spectrometry. Both virion types are pleomorphic with spherical morphology and have no significant difference in size despite rP18tri having denser particles. Both virion types also contain similar sets of cellular proteins. Among the highly enriched virion-associated cellular proteins are components of the endosomal sorting complex required for transport pathway and vesicle trafficking, such as ALIX, Tsg101, VPS, CHMP, and Ras-associated binding proteins, which have known functions in virus assembly and budding. Other enriched cellular proteins include peripheral and transmembrane proteins, chaperone proteins, and ribosomal proteins; their biological roles in viral infection warrant further analysis. Our study provides important insights into mammarenavirus particle formation and aids in the future development of viral vectors and antiviral discovery.IMPORTANCEMammarenaviruses, such as Lassa virus, are enveloped RNA viruses that can cause severe hemorrhagic fever diseases (Lassa fever) with no approved vaccine and limited therapeutic options. Cellular proteins incorporated into progeny virion particles and their biological roles in mammarenavirus infection have not been well characterized. Pichinde virus (PICV) is a prototypic mammarenavirus used as a surrogate model for Lassa fever. We used cryo-electron microscopy and proteomic analysis to characterize the morphology and protein contents of the purified PICV particles that package either two (bi-segmented) or three (tri-segmented) genomic RNA segments. Our results demonstrate a similar virion morphology but different particle density for the bi- and tri-segmented viral particles and reveal major virion-associated cellular proteins. This study provides important insights into the virus-host interactions that can be used for antiviral development and optimizing arenavirus-based vaccine vectors.

Dataset Information

Development of a Recombinant Pichinde Virus-Vectored Vaccine against Turkey Arthritis Reovirus and Its Immunological Response Characterization in Vaccinated Animals.

Publications

Development of a Recombinant Pichinde Virus-Vectored Vaccine against Turkey Arthritis Reovirus and Its Immunological Response Characterization in Vaccinated Animals.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets