Riemser Pharma (Germany)

BackgroundEfficacy studies are part of the regulatory requirements for obtaining marketing authorization for rabies virus vaccines intended for veterinary use. However, increasing emphasis on animal welfare and the application of the 3Rs principles (Replacement, Reduction, and Refinement) may prompt a critical reassessment of current standards for such studies. A substantial amount of data from numerous published experimental studies is available, which could be used to reconsider or refine existing specifications and protocols—particularly concerning observation periods post-infection (pi) and dose-finding studies.MethodsTo support this reassessment, we analyzed data from 289 published experimental studies. These studies covered both susceptibility and efficacy investigations across 16 mesocarnivorous target species considered for parenteral or oral rabies vaccination. The species represented seven taxonomic families or orders: Canidae, Didelphidae, Felidae, Herpestidae, Mephitidae, Musteloidea, and Procyonidae. The dataset included 1,171 records encompassing a total of 8,381 animals that had been vaccinated with either rabies virus (RABV) or non-RABV lyssaviruses. Parametric distributions (log-normal, Weibull, and gamma) were fitted to incubation periods to examine group differences. Additionally, multiple linear and logistic regression analyses were performed to identify key variables influencing incubation duration, post-infection survival, and inter-species differences among reservoir hosts.ResultsThe analyses revealed that viral strain, inoculation dose, and application site were consistently associated with incubation period length and mortality across most taxonomic groups. These variables significantly influenced incubation periods and survival rates post-infection. Notable differences were also observed between reservoir host species, highlighting the importance of species-specific factors in study design and interpretation.ConclusionsOur findings suggest that, in alignment with the 3Rs principle, existing animal models used in rabies vaccine efficacy research can be reconsidered and potentially refined. These refinements may not only enhance scientific validity but also contribute to ethical improvements in study design. Furthermore, the results may inform future risk assessments related to the importation of pets from rabies-endemic regions and support more humane, evidence-based approaches to vaccine evaluation.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12985-025-02996-0.

Abstract The 2020/2021 epidemic in Europe of highly pathogenic avian influenza virus (HPAIV) of subtype H5 surpassed all previously recorded European outbreaks in size, genotype constellations and reassortment frequency and continued into 2022 and 2023. The causative 2.3.4.4b viral lineage proved to be highly proficient with respect to reassortment with cocirculating low pathogenic AIV and seems to establish an endemic status in northern Europe. A specific HPAIV reassortant of the subtype H5N3 was detected almost exclusively in red knots (Calidris canutus islandica)in December 2020. It caused systemic and rapidly fatal disease leading to a singular and self-limiting mass mortality affecting about 3.500 birds in the German Wadden Sea, roughly 1% of the entire flyway population ofislandicared knots. Phylogenetic analyses revealed that the H5N3 reassortant very likely had formed in red knots and remained confined to this species. While mechanisms of virus circulation in potential reservoir species, dynamics of spill-over and reassortment events and the roles of environmental virus sources remain to be identified, the year-round infection pressure poses severe threats to endangered avian species, and prompts adaptation of habitat and species conservation practices.One-Sentence SummaryHigh red knot mortality in Europe (December 2020) was associated with infection of a unique genotype of HPAIV H5N3 clade 2.3.4.4b.

Abstract Emerging variants of concern (VOCs) drive the SARS-CoV-2 pandemic. We assessed VOC B.1.1.7, now prevalent in several countries, and VOC B.1.351, representing the greatest threat to populations with immunity to the early SARS-CoV-2 progenitors. B.1.1.7 showed a clear fitness advantage over the progenitor variant (wt-S614G) in ferrets and two mouse models, where the substitutions in the spike glycoprotein were major drivers for fitness advantage. In the “superspreader” hamster model, B.1.1.7 and wt-S614G had comparable fitness, whereas B.1.351 was outcompeted. The VOCs had similar replication kinetics as compared to wt-S614G in human airway epithelial cultures. Our study highlights the importance of using multiple models for complete fitness characterization of VOCs and demonstrates adaptation of B.1.1.7 towards increased upper respiratory tract replication and enhanced transmission in vivo.Summary sentenceB.1.1.7 VOC outcompetes progenitor SARS-CoV-2 in upper respiratory tract replication competition in vivo.

Classical swine fever virus (CSFV) C-strain “Riems” escape variants generated under selective antibody pressure with monoclonal antibodies and a peptide-specific antiserum in cell culture were investigated. Candidates with up to three amino acid exchanges in the immunodominant and highly conserved linear TAV-epitope of the E2-glycoprotein, and additional mutations in the envelope proteins ERNS and E1, were characterized both in vitro and in vivo.It was further demonstrated, that intramuscular immunization of weaner pigs with variants selected after a series of passages elicited full protection against lethal CSFV challenge infection. These novel CSFV C-strain variants with exchanges in the TAV-epitope present potential marker vaccine candidates. The DIVA (differentiating infected from vaccinated animals) principle was tested for those variants using commercially available E2 antibody detection ELISA. Moreover, direct virus differentiation is possible using a real-time RT-PCR system specific for the new C-strain virus escape variants or using differential immunofluorescence staining.

This study addressed the question of whether the collagen metabolism modulator cis-4-Hydroxy-L-proline (CHP) is applicable for potential use as a therapeutic inhibitor of pancreatic carcinoma cell growth. Cell proliferation, as well as quantification of apoptosis of murine Panc02 cells, was assessed after CHP treatment. Supplementary, the effect of CHP on tumor growth was examined in the subcutaneous Panc02 model in vivo. Mice received daily intraperitoneal injections of CHP (300, 400, and 500 mg/kg bw). In addition to the assessment of systemic parameters (blood count, enzyme activities), histology (HE) and immunohistochemistry (Ki-67) were performed from resected tumor specimens. Like reduction of metabolic activity, CHP also induced inhibition of cell growth in a dose-dependent manner, with however only slight increases in apoptosis. In vivo treatment of Panc02 tumors with CHP resulted in pronounced delay of tumor growth and decreases in tumor cell proliferation. Moreover, these effects were accompanied by a massive systemic leukocytosis as well increased leukocyte infiltration into the tumors subsequent to CHP therapy. CHP inhibits the proliferation of Panc02 tumor cells in a dose-dependent manner both in vitro and in vivo. Our presented data show that modulation of the collagen metabolism is an interesting strategy for treatment of pancreatic carcinoma.

Background:Aloe vera is a natural product that is frequently used in soothing skin care products such as aftersun lotions. In the present study we aimed to explore the anti-inflammatory potential of a highly concentrated A. vera gel in the UV erythema test in vivo. Methods: 40 volunteers with skin types II and III were included in the randomized, double-blind, placebo-controlled, phase III monocenter study. Test areas on the back were irradiated with the 1.5-fold minimal erythema dose of UVB. Subsequently, the test areas were treated occlusively on 2 subsequent days with A. vera gel (97.5%), the positive controls (0.25% prednicarbate, 1% hydrocortisone in placebo gel and 1% hydrocortisone cream) and a placebo gel. Erythema values were determined photometrically after 24 and 48 h. Results:A. vera gel (97.5%) significantly reduced UV-induced erythema after 48 h, being superior to 1% hydrocortisone in placebo gel. In contrast, 1% hydrocortisone in cream was more efficient than A. vera gel. Conclusions: In this study after 48 h the A. vera gel (97.5%) displayed some anti-inflammatory effects superior to those of 1% hydrocortisone in placebo gel. The A. vera gel tested here might be useful in the topical treatment of inflammatory skin conditions such as UV-induced erythema.

Newcastle disease virus (NDV) is a pathogen that is important in the poultry industry worldwide. Specifically, the virulent (velogenic) NDV is a particular threat because it has now occurred frequently worldwide. The outbreaks caused by highly virulent NDV in waterfowl and especially in goose flocks, have led to greater concern in recent years as aquatic birds were previously resistant to most virulent NDV strains from chickens. The molecular determinants of host tropism, virulence and emergence of NDV isolated from diseased goose flocks are poorly understood. In the present study, we rescued a highly virulent NDV isolated from a goose using the reverse genetics approach. Infectious virus was successfully generated by cotransfection of a full-length cDNA clone of the NDV strain ZJ1 with helper plasmids. The recombinant NDV was indistinguishable from the parental wild-type virus with respect to its growth kinetics in cell culture as well as its biological properties. A recombinant NDV expressing green fluorescent protein (GFP) was generated, and GFP was subsequently detected in cells and various organs from the infected chickens.