Publications by authors named "Ralf Amann"

Article Synopsis
  • The Prime-2-CoV_Beta is a new COVID-19 vaccine designed to target the SARS-CoV-2 spike and nucleocapsid antigens, and was tested in a phase I clinical trial involving 60 healthy adults in Germany from June 2022 to June 2023.
  • The trial showed that the vaccine had a good safety profile with only mild to moderate side effects, such as pain at the injection site, fatigue, and headache, and no serious adverse events were reported.
  • Immunization resulted in strong immune responses, particularly at higher doses, leading to significant increases in antibodies against SARS-CoV-2 and its variants, indicating the vaccine's potential for broader protection
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Among the common strategies to design next-generation COVID-19 vaccines is broadening the antigenic repertoire thereby aiming to increase efficacy against emerging variants of concern (VoC). This study describes a new Orf virus-based vector (ORFV) platform to design a multiantigenic vaccine targeting SARS-CoV-2 spike and nucleocapsid antigens. Vaccine candidates were engineered, either expressing spike protein (ORFV-S) alone or co-expressing nucleocapsid protein (ORFV-S/N).

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Article Synopsis
  • Next-generation COVID-19 vaccines aim to improve coverage against existing and future variants while extending protection duration; the Prime-2-CoV_Beta vaccine uses an ORF virus platform to present multiple antigens.
  • A phase 1 trial (ORFEUS study) tested the safety and immune response of Prime-2-CoV_Beta in participants aged 18-55 and 65-85 who previously received mRNA vaccines, with doses administered on day 1 and day 29.
  • Results showed that Prime-2-CoV_Beta is safe, well tolerated, and generates strong immune responses, especially in younger participants, suggesting the ORFV platform's potential for future vaccine development.
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Viral vector vaccines represent a substantial advancement in immunization technology, offering numerous benefits over traditional vaccine modalities. The Orf virus (ORFV) strain D1701-VrV is a particularly promising candidate for vaccine development due to its distinctive attributes, such as a good safety profile, the ability to elicit both humoral and cellular immunity, and its favorable genetic and thermal stability. Despite ORFV's theoretical safety advantages, such as its narrow host range and limited systemic spread post-inoculation, a critical gap persists between these theoretical benefits and the empirical evidence regarding its in vivo safety profile.

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Article Synopsis
  • Prime-2-CoV_Beta is a new COVID-19 vaccine candidate that uses an Orf virus to express the nucleocapsid and spike proteins from SARS-CoV-2, specifically the Beta strain.
  • In Phase I clinical trials, the vaccine was found to be safe and able to generate immune responses, but further studies were needed due to the evolving variants, particularly Omicron.
  • Research in mice and hamsters showed that while Prime-2-CoV_Beta elicited strong immune responses in unvaccinated animals, it did not significantly boost immunity in already immunized subjects and demonstrated similar protection levels between different immunization strategies.
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Article Synopsis
  • The Orf virus (ORFV) is a notable candidate for vaccines against diseases and cancer, with ongoing clinical testing, necessitating a clarification step during its production.
  • This study explored various filtering options in a high-throughput setting, determining that polypropylene-based Sartopure® PP3 filters are the most effective for improving ORFV recovery.
  • Key factors influencing ORFV yields were identified, including optimal harvest timing and the use of nucleases, leading to a more efficient and scalable clarification process crucial for vaccine development.
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The Orf virus (ORFV) is a promising candidate for vector vaccines as well as for immunomodulatory and oncolytic therapies. However, few publications are available on its infectivity degradation or on suitable additives for prolonging its viral stability. In this study, the non-supplemented ORFV itself showed a very high stability at storage temperatures up to 28 °C, with a linear titer loss of 0.

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A promising new vaccine platform is based on the Orf virus, a viral vector of the genus Parapoxvirus, which is currently being tested in phase I clinical trials. The application as a vaccine platform mandates a well-characterised, robust, and efficient production process. To identify critical process parameters in the production process affecting the virus' infectivity, the Orf virus was subjected to forced degradation studies, including thermal, pH, chemical, and mechanical stress conditions.

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Steric exclusion chromatography (SXC) is a promising purification method for biological macromolecules such as the Orf virus (ORFV) vector. The method's principle is closely related to conventional polyethylene glycol (PEG) precipitation, repeatedly implementing membranes as porous chromatographic media. In the past decade, several purification tasks with SXC showed exceptionally high yields and a high impurity removal.

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Article Synopsis
  • - The study explores various methods for purifying biological nanoparticles, specifically focusing on the Orf virus (ORFV), to determine their electrostatic charge while ensuring sample quality and efficiency.
  • - Three purification techniques were evaluated: (I) steric exclusion chromatography (SXC), (II) SXC with centrifugal diafiltration, and (III) sucrose cushion ultracentrifugation, all achieving over 99% protein removal and comparable sample quality.
  • - Among the methods, SXC (I) showed a quick operation time and ease of use, making it a strong candidate for preparing samples for physicochemical analysis of viruses.
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The pore-forming inflammatory cell death pathway, pyroptosis, was first described in the early 1990s and its role in health and disease has been intensively studied since. The effector molecule GSDMD is cleaved by activated caspases, mainly Caspase 1 or 11 (Caspase 4/5 in humans), downstream of inflammasome formation. In this review, we describe the molecular events related to GSDMD-mediated pore formation.

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Background: Orf virus (ORFV)-based vectors are attractive for vaccine development as they enable the induction of potent immune responses against specific transgenes. Nevertheless, the precise mechanisms of immune activation remain unknown. This study therefore aimed to characterize underlying mechanisms in human immune cells.

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Although dengue virus (DENV) affects almost half of the world's population there are neither preventive treatments nor any long-lasting and protective vaccines available at this time. The complexity of the protective immune response to DENV is still not fully understood. The most advanced vaccine candidates focus specifically on humoral immune responses and the production of virus-neutralizing antibodies.

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The large demand for safe and efficient viral vector-based vaccines and gene therapies against both inherited and acquired diseases accelerates the development of viral vectors. One outstanding example, the Orf virus, has a wide range of applications, a superior efficacy and an excellent safety profile combined with a reduced pathogenicity compared to other viral vectors. However, besides these favorable attributes, an efficient and scalable downstream process still needs to be developed.

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In recent years, the Orf virus has become a promising tool for protective recombinant vaccines and oncolytic therapy. However, suitable methods for an Orf virus production, including up- and downstream, are very limited. The presented study focuses on downstream processing, describing the evaluation of different chromatographic unit operations.

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The potency of viral vector-based vaccines depends on their ability to induce strong transgene-specific immune response without triggering anti-vector immunity. Previously, (ORFV, ) strain D1701-V was reported as a novel vector mediating protection against viral infections. The short-lived ORFV-specific immune response and the absence of virus neutralizing antibodies enables repeated immunizations and enhancement of humoral immune responses against the inserted antigens.

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Parrot bornaviruses (PaBVs) are the causative agents of proventricular dilatation disease (PDD), a chronic and often fatal neurologic disorder in Psittaciformes. The disease is widely distributed in private parrot collections and threatens breeding populations of endangered species. Thus, immunoprophylaxis strategies are urgently needed.

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The (ORFV; ) strain D1701 with an attenuated phenotype and excellent immunogenic capacity is successfully used for the generation of recombinant vaccines against different viral infections. Adaption for growth in Vero cells was accompanied by additional major genomic changes resulting in ORFV strain variant D1701-V. In this study, restriction enzyme mapping, blot hybridization and DNA sequencing of the deleted region s (A, AT and D) in comparison to the predecessor strain D1701-B revealed the loss of 7 open reading frames (ORF008, ORF101, ORF102, ORF114, ORF115, ORF116, ORF117).

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Orf virus (ORFV) is an epitheliotropic poxvirus, which belongs to the genus Parapoxvirus. Among them the highly attenuated, apathogenic strain D1701-V is regarded as a promising candidate for novel virus vector vaccines. Our recent work demonstrated that those ORFV-based recombinants were able to induce protective, long-lasting immunity in various hosts that are non-permissive for ORFV.

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Previously we demonstrated the versatile utility of the Parapoxvirus Orf virus (ORFV) as a vector platform for the development of potent recombinant vaccines. In this study we present the generation of new ORFV recombinants expressing the hemagglutinin (HA) or nucleoprotein (NP) of the highly pathogenic avian influenza virus (HPAIV) H5N1. Correct foreign gene expression was examined in vitro by immunofluorescence, Western blotting and flow cytometry.

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The present study describes the generation of a new Orf virus (ORFV) recombinant, D1701-V-RabG, expressing the rabies virus (RABV) glycoprotein that is correctly presented on the surface of infected cells without the need of replication or production of infectious recombinant virus. One single immunization with recombinant ORFV can stimulate high RABV-specific virus-neutralizing antibody (VNA) titers in mice, cats, and dogs, representing all nonpermissive hosts for the ORFV vector. The protective immune response against severe lethal challenge infection was analyzed in detail in mice using different dosages, numbers, and routes for immunization with the ORFV recombinant.

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