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The Journal of Dairy Research Nov 2023Dairy products are major sources of high-quality protein and bioavailable nutrients and dairy production contributes to local, regional and national-level economies.... (Review)
Review
Dairy products are major sources of high-quality protein and bioavailable nutrients and dairy production contributes to local, regional and national-level economies. Consumption of raw milk and raw milk products does, however, carry a zoonotic risk, as does direct contact with cattle by farm husbandry staff and other employees. This review will mainly focus on the latter, and deal with it from the standpoint of a well-developed dairy industry, using the example of the Netherlands. With regard to dairy cattle, the main bacterial pathogens are spp., and as well as and . The main viral pathogens associated with dairy are Rift Valley fever virus, rabies virus, cowpox virus and vaccinia virus. The main parasitological infections are and , however, the last mentioned have mainly swimming pools as sources of human infection. Finally ectoparasites such as lice and mites and may affect employees. Some pathogens may cause health problems due to contamination. Bacterial pathogens of importance that may contaminate milk are subsp. , . Excretion of zoonotic viruses in milk is negligible in the Netherlands, and the endoparasite, is mainly found in suckling and fattening calves, whilst the risk in dairy cattle is limited. Excretion of transmissible spongiform encephalopathies (TSEs) or mycoses in milk are not expected and are, therefore, not of importance here.Being aware of the risks and working according to hygiene standards can substantially limit zoonotic risks for employees. Additionally, diseased employees are advised to limit their contact with cattle and to indicate that they work with cattle when consulting a physician. To prevent zoonotic risks through excretion of pathogens in milk, standard hygiene measures are necessary. Further, using only pasteurised milk for consumption and/or processing of milk can considerably limit the risks. If these measures are not possible, well-constructed monitoring can be followed. Monitoring programmes already exist for pathogens such as for and subsp. . For others, like programmes are not available yet as far as we know.
Topics: Cattle; Humans; Animals; Escherichia coli; Milk; Cryptosporidiosis; Cryptosporidium; Mycobacterium avium subsp. paratuberculosis; Listeria monocytogenes; Cattle Diseases
PubMed: 38186208
DOI: 10.1017/S0022029923000730 -
Nature Communications Sep 2023In early 2022, a cluster of monkeypox virus (MPXV) infection (mpox) cases were identified within the UK with no prior travel history to MPXV-endemic regions....
In early 2022, a cluster of monkeypox virus (MPXV) infection (mpox) cases were identified within the UK with no prior travel history to MPXV-endemic regions. Subsequently, case numbers exceeding 80,000 were reported worldwide, primarily affecting gay, bisexual, and other men who have sex with men (GBMSM). Public health agencies worldwide have offered the IMVANEX Smallpox vaccination to these individuals at high-risk to provide protection and limit the spread of MPXV. We have developed a comprehensive array of ELISAs to study poxvirus-induced antibodies, utilising 24 MPXV and 3 Vaccinia virus (VACV) recombinant antigens. Panels of serum samples from individuals with differing Smallpox-vaccine doses and those with prior MPXV infection were tested on these assays, where we observed that one dose of Smallpox vaccination induces a low number of antibodies to a limited number of MPXV antigens but increasing with further vaccination doses. MPXV infection induced similar antibody responses to diverse poxvirus antigens observed in Smallpox-vaccinated individuals. We identify MPXV A27 as a serological marker of MPXV-infection, whilst MPXV M1 (VACV L1) is likely IMVANEX-specific. Here, we demonstrate analogous humoral antigen recognition between both MPXV-infected or Smallpox-vaccinated individuals, with binding to diverse yet core set of poxvirus antigens, providing opportunities for future vaccine (e.g., mRNA) and therapeutic (e.g., mAbs) design.
Topics: Male; Humans; Monkeypox virus; Smallpox; Immunity, Humoral; Homosexuality, Male; Sexual and Gender Minorities; Smallpox Vaccine
PubMed: 37741831
DOI: 10.1038/s41467-023-41587-x -
Journal of Controlled Release :... Nov 2023Delivering large therapeutic molecules via the blood-brain barrier to treat ischemic stroke remains challenging. NR2B9c is a potent neuroprotective peptide but it's safe...
Delivering large therapeutic molecules via the blood-brain barrier to treat ischemic stroke remains challenging. NR2B9c is a potent neuroprotective peptide but it's safe and targeted delivery to the brain requires an efficient, natural, and non-immunogenic delivery technique. Small extracellular vesicles (sEVs) have shown great potential as a non-immunogenic, natural cargo delivery system; however, tailoring of its inefficient brain targeting is desired. Here, we coupled rabies virus glycoprotein 29 with sEVs surface via bio-orthogonal click chemistry reactions, followed by loading of NR2B9c, ultimately generating stroke-specific therapeutic COCKTAIL (sEVs-COCKTAIL). Primary neurons and Neuro-2a cells were cultured for in vitro and transient middle cerebral artery occlusion model was used for in vivo studies to evaluate neuron targeting and anti-ischemic stroke potential of the sEVs-COCKTAIL. Bio-clickable sEVs were selectively taken up by neurons but not glial cells. In the in vitro ischemic stroke model of oxygen-glucose deprivation, the sEVs-COCKTAIL exhibited remarkable potential against reactive oxygen species and cellular apoptosis. In vivo studies further demonstrated the brain targeting and increased half-life of bio-clickable sEVs, delivering NR2B9c to the ischemic brain and reducing stroke injury. Treatment with the sEVs-COCKTAIL significantly increased behavioral recovery and reduced neuronal apoptosis after transient middle cerebral artery occlusion. NR2B9c was delivered to neurons binding to post-synaptic density protein-95, inhibiting N-methyl-d-Aspartate receptor-mediated over production of oxidative stress and mitigating protein B-cell lymphoma 2 and P38 proteins expression. Our results provide an efficient and biocompatible approach to a targeted delivery system, which is a promising modality for stroke therapy.
Topics: Humans; Brain Ischemia; Ischemic Stroke; Infarction, Middle Cerebral Artery; Stroke; Extracellular Vesicles
PubMed: 37793483
DOI: 10.1016/j.jconrel.2023.10.003 -
Human Vaccines & Immunotherapeutics Dec 2023This phase III clinical trial aimed to assess the safety and demonstrate the immunogenicity of a candidate freeze-dried purified Vero cell-based rabies vaccine... (Randomized Controlled Trial)
Randomized Controlled Trial
This phase III clinical trial aimed to assess the safety and demonstrate the immunogenicity of a candidate freeze-dried purified Vero cell-based rabies vaccine (PVRV-WIBP) developed for human use. A cohort of 40 participants in stage 1 and 1956 subjects in stage 2 with an age range of 10-50 years were recruited for the phase III clinical trial. For safety analysis in stage 1, 20 participants received either 4-dose or 5-dose regimen of PVRV-WIBP. In stage 2, 1956 subjects were randomly divided into the 5-dose PVRV-WIBP, 5-dose PVRV-LNCD, and 4-dose PVRV-WIBP groups. The serum neutralizing antibody titer against rabies was determined on day 7 or 14 and day 35 or 42. Adverse reactions were recorded for more than 6 months. Most adverse reactions, which were mild and moderate in severity, occurred and resolved within 1 week after each injection in the PVRV-WIBP (4 and 5 doses) and PVRV-LNCD (5 doses) groups. All three groups achieved complete seroconversion 14 days after the initial dose and 14 days after completing the full vaccination schedule, the susceptible subjects in the PVRV-WIBP group (4-dose or 5-dose regimen) displayed higher neutralizing antibody titers against the rabies virus compared to those in the PVRV-LNCD group (5-dose regimen). PVRV-WIBP induced non-inferior immune responses versus PVRV-LNCD as assessed by seroconversion rate. PVRV-WIBP was well tolerated and non-inferior to PVRV-LNCD in healthy individuals aged 10-50 years. The results indicated that PVRV-WIBP (both 4- and 5-dose schedules) could be an alternative to rabies post-exposure prophylaxis.
Topics: Animals; Chlorocebus aethiops; Humans; Child; Adolescent; Young Adult; Adult; Middle Aged; Rabies Vaccines; Rabies; East Asian People; Antibodies, Viral; Rabies virus; Antibodies, Neutralizing; Vero Cells; HIV Seropositivity; Immunogenicity, Vaccine
PubMed: 37249318
DOI: 10.1080/21645515.2023.2211896 -
Nature Methods Mar 2024
Topics: Neurons; Rabies virus
PubMed: 38472461
DOI: 10.1038/s41592-024-02220-x -
Clinical Infectious Diseases : An... Sep 2023All World Health Organization (WHO) pre-qualified rabies vaccines for humans are inactivated tissue culture rabies virus formulations produced for intramuscular (IM)...
Side-by-side Comparative Study of the Immunogenicity of the Intramuscular and Intradermal Rabies Post-exposure Prophylaxis Regimens in a Cohort of Suspected Rabies Virus Exposed Individuals.
All World Health Organization (WHO) pre-qualified rabies vaccines for humans are inactivated tissue culture rabies virus formulations produced for intramuscular (IM) administration. Due to costs and vaccine shortage, dose-saving intradermal (ID) administration of rabies post-exposure prophylaxis (PEP) is encouraged by WHO. This study compared the immunogenicity of the ID 2-site, 3-visit Institut Pasteur Cambodge (IPC) PEP regimen to the IM 1-site, 4-visit 4-dose Essen regimen using Verorab vaccine (Sanofi). The development of neutralizing antibodies (nAbs) and T cell response was assessed in 210 patients with a category II or III animal exposure in a rabies-endemic country. At day 28, all participants developed nAbs (≥0.5 IU/mL), irrespective of PEP scheme, age, or administration of rabies immunoglobulin. T cell response and nAb titers were similar for both PEP schemes. This study demonstrated that the 1-week ID IPC regimen is as effective as the 2-week IM 4-dose Essen regimen in inducing an anti-rabies immune response under real-life PEP.
Topics: Animals; Humans; Rabies Vaccines; Rabies virus; Post-Exposure Prophylaxis; Injections, Intramuscular; Rabies; Antibodies, Neutralizing; Injections, Intradermal; Antibodies, Viral
PubMed: 37337899
DOI: 10.1093/cid/ciad304 -
Microbiology Spectrum Sep 2023Rabies kills more than 59,000 people annually, mainly in developing countries. Previous studies on the evolution and distribution of rabies viruses (RABVs) were...
Rabies kills more than 59,000 people annually, mainly in developing countries. Previous studies on the evolution and distribution of rabies viruses (RABVs) were scattered. Here, we explore the evolution and distribution of this deadly virus from a novel panorama view. Multiple bioinformatic software tools were employed to analyze the phylogenetic diversity, evolution, spatiotemporal, and distribution of RABVs. The analyses were based on 1,202 qualified full-length genomes of RABVs and numerous literatures. Of the 10 distinct phylogenetic clades of RABV that we identified, more frequent intra- and inter-clade recombination occurs in the sequences of Asian-SEA, Arctic, and Cosmopolitan clades isolated from China, while according to existing sequence information, RABV might originate from bats (posterior probability, PP = 0.75, PP = 0.60 inferred from N and L genes, separately) in North America (PP = 0.57, PP = 0.62 inferred from N and L genes, separately). Due to the difference in evolutionary rate of N (2.22 × 10 subs/site/year, 95% HPD 1.99-2.47 × 10 subs/site/year) and L genes (1.67 × 10 subs/site/year, 95% HPD 1.59-1.74 × 10 subs/site/year), the root age was 1,406.6 (95% HPD 1,291.2-1,518.2) and 1,122.7 (95% HPD 1,052.4-1,193.9) inferred from N and L genes, separately. Among other findings, Mephitidae plays an important role in the interspecific transmission and communication of RABV, which we found tends to spread to populations genetically proximate to the host. We also identified amino acids under positive selection in different genes of different clades as well as single nucleotide variation sites important for different lineages. IMPORTANCE Rabies virus is widely distributed all over the world, and wild animals are its largest potential reservoir. Our study offers a panorama view about evolution and distribution of rabies viruses and emphasizes the need to monitor the transmission dynamics of animal rabies.
PubMed: 37668395
DOI: 10.1128/spectrum.05257-22 -
Viruses May 2024Seroprevalence of lyssaviruses in certain bat species has been proven in the Republic of Croatia, but there have been no confirmed positive bat brain isolates or human...
Seroprevalence of lyssaviruses in certain bat species has been proven in the Republic of Croatia, but there have been no confirmed positive bat brain isolates or human fatalities associated with bat injuries/bites. The study included a retrospective analysis of bat injuries/bites, post-exposure prophylaxis (PEP) and geographic distribution of bat injuries in persons examined at the Zagreb Antirabies Clinic, the Croatian Reference Centre for Rabies. In the period 1995-2020, we examined a total of 21,910 patients due to animal injuries, of which 71 cases were bat-related (0.32%). Of the above number of patients, 4574 received rabies PEP (20.87%). However, for bat injuries, the proportion of patients receiving PEP was significantly higher: 66 out of 71 patients (92.95%). Of these, 33 received only the rabies vaccine, while the other 33 patients received the vaccine with human rabies immunoglobulin (HRIG). In five cases, PEP was not administered, as there was no indication for treatment. Thirty-five of the injured patients were biologists or biology students (49.29%). The bat species was confirmed in only one of the exposure cases. This was a serotine bat (Eptesicus serotinus), a known carrier of . The results showed that the bat bites were rather sporadic compared to other human injuries caused by animal bites. All bat injuries should be treated as if they were caused by a rabid animal, and according to WHO recommendations. People who come into contact with bats should be strongly advised to be vaccinated against rabies. Entering bat habitats should be done with caution and in accordance with current recommendations, and nationwide surveillance should be carried out by competent institutions and in close collaboration between bat experts, epidemiologists and rabies experts.
Topics: Rabies; Chiroptera; Humans; Animals; Post-Exposure Prophylaxis; Croatia; Female; Bites and Stings; Adult; Male; Retrospective Studies; Middle Aged; Young Adult; Rabies Vaccines; Adolescent; Child; Rabies virus; Aged; Child, Preschool; Seroepidemiologic Studies; Lyssavirus
PubMed: 38932168
DOI: 10.3390/v16060876 -
Translational Research : the Journal of... Sep 2023Chimeric antigen receptor T cell (CAR-T) therapy has limited efficacy for treating glioma because of the infiltrative nature of the blood-brain barrier (BBB) and T cell...
Chimeric antigen receptor T cell (CAR-T) therapy has limited efficacy for treating glioma because of the infiltrative nature of the blood-brain barrier (BBB) and T cell exhaustion. Conjugation with rabies virus glycoprotein (RVG) 29 enhances the brain-related efficacy of various agents. Here we assess whether RVG enhances the ability of CAR-T cells to cross the BBB and improves their immunotherapy. We generated 70R CAR-T cells (anti-CD70 CAR-T modified with RVG29) and validated their tumor-killing efficacy in vitro and in vivo. We validated their effects on tumor regression in a human glioma mouse orthotopic xenograft model as well as in patient-derived orthotopic xenograft (PDOX) models. The signaling pathways activated in 70R CAR-T cells were revealed by RNA sequencing. The 70R CAR-T cells we generated showed effective antitumor function against CD70 glioma cells both in vitro and in vivo. 70R CAR-T cells were better able to cross the BBB into the brain than CD70 CAR-T cells under the same treatment conditions. Moreover, 70R CAR-T cells significantly promote the regression of glioma xenografts and improve the physical characteristics of mice without causing overt adverse effects. RVG modification enables CAR-T cells to cross the BBB, and stimulation with glioma cells induces 70R CAR-T cells to expand in a resting state. The modification of RVG29 has a positive impact on CAR-T therapy for brain tumors and may have potential in CAR-T therapy for glioma.
Topics: Humans; Animals; Mice; Receptors, Chimeric Antigen; Rabies virus; Glioma; Glycoproteins; Immunotherapy, Adoptive; Xenograft Model Antitumor Assays; Cell Line, Tumor
PubMed: 36977441
DOI: 10.1016/j.trsl.2023.03.003 -
Emerging Microbes & Infections Dec 2024During the COVID-19 epidemic, the incidence of rabies has increased in several countries, especially in remote and disadvantaged areas, due to inadequate surveillance...
During the COVID-19 epidemic, the incidence of rabies has increased in several countries, especially in remote and disadvantaged areas, due to inadequate surveillance and declining immunization coverage. Multiple vaccinations with inactivated rabies virus vaccines for pre- or post-exposure prophylaxis are considered inefficient, expensive and impractical in developing countries. Herein, three modified human recombinant adenoviruses type 5 designated Adv-RVG, Adv-E1-RVG, and Adv-RVDG, carrying rabies virus G (RVG) expression cassettes in various combinations within or genomic regions, were constructed to serve as rabies vaccine candidates. Adv-RVDG mediated greater RVG expression both and and induced a more robust and durable humoral immune response than the rabies vaccine strain SAD-L16, Adv-RVG, and Adv-E1-RVG by more effectively activating the dendritic cells (DCs) - follicular helper T (Tfh) cells - germinal centre (GC) / memory B cells (MBCs) - long-lived plasma cells (LLPCs) axis with 100% survival after a lethal RABV challenge in mice during the 24-week study period. Similarly, dogs and cats immunized with Adv-RVDG showed stronger and longer-lasting antibody responses than those vaccinated with a commercial inactivated rabies vaccine and showed good tolerance to Adv-RVDG. In conclusion, our study demonstrated that simultaneous insertion of protective antigens into the and genomic regions of adenovirus vector can significantly enhance the immunogenicity of adenoviral-vectored vaccines, providing a theoretical and practical basis for the subsequent development of multivalent and multi-conjugated vaccines using recombinant adenovirus platform. Meanwhile, our data suggest Adv-RVDG is a safe, efficient, and economical vaccine for mass-coverage immunization.
Topics: Cats; Dogs; Humans; Animals; Mice; Rabies virus; Rabies Vaccines; Immunity, Humoral; Cat Diseases; Antibodies, Viral; Dog Diseases; Adenoviridae
PubMed: 38164714
DOI: 10.1080/22221751.2023.2300461