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Diagnoses of infectious diseases are being transformed as mass self‐testing using rapid antigen tests (RATs) is increasingly integrated into public health. Widely used during the COVID‐19 pandemic, RATs are claimed to have many advantages over 'gold‐standard' polymerase chain reaction tests, especially their ease of use and production of quick results. Yet, while laboratory studies indicate the value of RATs in detecting the SARS‐CoV‐2 virus antigen, uncertainty surrounds their deployment and ultimate effectiveness in stemming infections. This article applies the analytic lens of biological citizenship (or bio‐citizenship) to explore Australia's experience of implementing a RAT‐based mass self‐testing strategy to manage COVID‐19. Drawing on Annemarie Mol's (1999, The Sociological Review, 47(1), 74–89) concept of ontological politics and analysing government statements, scientific articles and news media reporting published during a critical juncture of the strategy's implementation, we explore the kind of bio‐citizenship implied by this strategy. Our analysis suggests the emergence of what we call liminal bio‐citizenship, whereby citizens are made responsible for self‐managing infection risk without the diagnostic certitude this demands. We discuss how the different realities of mass self‐testing interact to reinforce this liminal citizenship and consider the implications for the sociology of diagnosis. [ABSTRACT FROM AUTHOR]

Feline infectious peritonitis (FIP) is a multisystemic, generally lethal immuno-inflammatory disease of domestic cats caused by an infection with a genetic variant of feline coronavirus, referred to as the FIP virus (FIPV). We leveraged data from four different antiviral clinical trials performed at the University of California, Davis. Collectively, a total of 60 client-owned domestic cats, each with a confirmed diagnosis of naturally occurring FIP, were treated with a variety of antiviral compounds. The tested therapies included the antiviral compounds GS-441524, remdesivir, molnupiravir and allogeneic feline mesenchymal stem/stroma cell transfusions. Four client-owned cats with FIP did not meet the inclusion criteria for the trials and were not treated with antiviral therapies; these cats were included in the data set as untreated FIP control cats. ELISA and Western blot assays were performed using feline serum/plasma or ascites effusions obtained from a subset of the FIP cats. Normalized tissue/effusion viral loads were determined in 34 cats by a quantitative RT-PCR of nucleic acids isolated from either effusions or abdominal lymph node tissue. Twenty-one cats were PCR "serotyped" (genotyped) and had the S1/S2 region of the coronaviral spike gene amplified, cloned and sequenced from effusions or abdominal lymph node tissue. In total, 3 untreated control cats and 14 (23.3%) of the 60 antiviral-treated cats died or were euthanized during (13) or after the completion of (1) antiviral treatment. Of these 17 cats, 13 had complete necropsies performed (10 cats treated with antivirals and 3 untreated control cats). We found that anticoronaviral serologic responses were persistent and robust throughout the treatment period, primarily the IgG isotype, and focused on the viral structural Nucleocapsid and Membrane proteins. Coronavirus serologic patterns were similar for the effusions and serum/plasma of cats with FIP and in cats entering remission or that died. Viral RNA was readily detectable in the majority of the cats in either abdominal lymph node tissue or ascites effusions, and all of the viral isolates were determined to be serotype I FIPV. Viral nucleic acids in cats treated with antiviral compounds became undetectable in ascites or abdominal lymph node tissue by 11 days post-treatment using a sensitive quantitative RT-PCR assay. The most common pathologic lesions identified in the necropsied cats were hepatitis, abdominal effusion (ascites), serositis, pancreatitis, lymphadenitis, icterus and perivasculitis. In cats treated with antiviral compounds, gross and histological lesions characteristic of FIP persisted for several weeks, while the viral antigen became progressively less detectable. [ABSTRACT FROM AUTHOR]

Since the foot-and-mouth disease (FMD) outbreak in South Korea in 2010–2011, vaccination policies utilizing inactivated FMD vaccines composed of types O and A have been implemented nationwide. However, because type Asia1 occurred in North Korea in 2007 and intermittently in neighboring countries, the risk of type Asia1 introduction cannot be ruled out. This study evaluated the antigen yield and viral inactivation kinetics of the recombinant Asia1 Shamir vaccine strain (Asia1 Shamir-R). When Asia1 Shamir-R was proliferated in shaking flasks (1 L), a 2 L bioreactor (1 L), and a wave bioreactor (25 L), the antigen yields were 7.5 μg/mL, 5.2 μg/mL, and 3.8 μg/mL, respectively. The optimal FMDV inactivation conditions were 2 mM BEI at 26 °C and 1.0 mM BEI at 37 °C. There was no antigen loss due to BEI treatment, and only a decrease in antigen levels was observed during storage. The sera from pigs immunized with antigen derived from a bioreactor exhibited a neutralizing antibody titer of approximately 1/1000 against Asia1 Shamir and Asia1/MOG/05 viruses; therefore, Asia1 Shamir-R is expected to provide sufficient protection against both viruses. If an FMD vaccine production facility is established, this Asia1 Shamir-R can be employed for domestic antigen banks in South Korea. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS), a tick-borne zoonotic disease, is caused by infection with SFTS virus (SFTSV). A previous study reported that human-to-human direct transmission of SFTSV can occur. However, potential animal-to-animal transmission of SFTSV without ticks has not been fully clarified. Thus, the objective of this study was to investigate potential mice-to-mice transmission of SFTSV by co-housing three groups of mice [i.e., wild-type mice (WT), mice injected with an anti-type I interferon-α receptor-blocking antibody (IFNAR Ab), and mice with knockout of type I interferon-α receptor (IFNAR KO)] as spreaders or recipients with different immune competence. As a result, co-housed IFNAR Ab and IFNAR KO mice showed body weight loss with SFTS viral antigens detected in their sera, extracorporeal secretions, and various organs. Based on histopathology, white pulp atrophy in the spleen was observed in all co-housed mice except WT mice. These results obviously show that IFNAR Ab and IFNAR KO mice, as spreaders, exhibited higher transmissibility to co-housed mice than WT mice. Moreover, IFNAR KO mice, as recipients, were more susceptible to SFTSV infection than WT mice. These findings suggest that type I interferon signaling is a pivotal factor in mice intraspecies transmissibility of SFTSV in the absence of vectors such as ticks. [ABSTRACT FROM AUTHOR]

The African swine fever virus (ASFV) mutant ASFV-G-∆I177L is a safe and efficacious vaccine which induces protection against the challenge of its parental virus, the Georgia 2010 isolate. Although a genetic DIVA (differentiation between infected and vaccinated animals) assay has been developed for this vaccine, still there is not a serological DIVA test for differentiating between animals vaccinated with ASFV-G-∆I177L and those infected with wild-type viruses. In this report, we describe the development of the ASFV-G-∆I177L mutant having deleted the EP402R gene, which encodes for the viral protein responsible for mediating the hemadsorption of swine erythrocytes. The resulting virus, ASFV-G-∆I177L/∆EP402R, does not have a decreased ability to replicates in swine macrophages when compared with the parental ASFV-G-∆I177L. Domestic pigs intramuscularly (IM) inoculated with either 102 or 106 HAD50 of ASFV-G-∆I177L/∆EP402R remained clinically normal, when compared with a group of mock-vaccinated animals, indicating the absence of residual virulence. Interestingly, an infectious virus could not be detected in the blood samples of the ASFV-G-∆I177L/∆EP402R-inoculated animals in either group at any of the time points tested. Furthermore, while all of the mock-inoculated animals presented a quick and lethal clinical form of ASF after the intramuscular inoculation challenge with 102 HAD50 of highly virulent parental field isolate Georgia 2010 (ASFV-G), all of the ASFV-G-∆I177L/∆EP402R-inoculated animals were protected, remaining clinically normal until the end of the observational period. Most of the ASFV-G-∆I177L/∆EP402R-inoculated pigs developed strong virus-specific antibody responses against viral antigens, reaching maximum levels at 28 days post inoculation. Importantly, all of the sera collected at that time point in the ASFV-G-∆I177L/∆EP402R-inoculated pigs did not react in a direct ELISA coated with the recombinant EP402R protein. Conversely, the EP402R protein was readily recognized by the pool of sera from the animals immunized with recombinant live attenuated vaccine candidates ASFV-G-∆I177L, ASFV-G-∆MGF, or ASFV-G-∆9GL/∆UK. Therefore, ASFV-G-∆I177L/∆EP402R is a novel, safe and efficacious candidate with potential to be used as an antigenically DIVA vaccine. [ABSTRACT FROM AUTHOR]

The article comments on the development of a standardized, laboratory result-based hepatitis C virus (HCV) clearance cascade for public health jurisdictions. It identifies elements for constructing a population-level HCV cascade, as well as the important data-to-share opportunities measured by a laboratory result-based HCV cascade. It informs about the funding to support health departments to implement laboratory result-based HCV cascades and cites limitations of HCV cascade.

Nanotechnology products such as titanium dioxide nanoparticles (TiO2-NPs) can be used for viral infections because of their unique characteristics. The current study aimed to determine the impact of TiO2-NPs on HPV type 1 and 2 infections. The characterization of these NPs was performed using dynamic light scattering (DLS), field emission scanning electron microscopy (FESEM), high-resolution transmission electron microscopy (HRTEM), and X-ray diffraction (XRD). The MTT assay was used to determine the toxic impacts of TiO2-NPs on BHK-21 cells. The efficiency of TiO2-NPs was performed using several parameters, including TCID50 and RT-PCR assays. An indirect immunofluorescence assay (IFA) was performed to estimate the inhibitory impact of TiO2-NPs on viral antigen expression, and Acyclovir was used as a reference medicine. When the human papilloma type 1 and 2 viruses exposed to TiO2-NPs at high doses (100 μg/mL) produced 0.3, 1.1, 2.3, and 3.3 log10 TCID50 decreases in infective virus load when compared with control viruses (P<0.0001), these TiO2-NPs doses were related to 24.9%, 35.1%, 47.2%, 59.5%, and 66.6% inhibition percentages that were determined depending on the viral titer as compared to virus control. It is concluded that TiO2-NPs have strong potential for the treatment of face and labial lesions caused by papillomaviruses 1 and 2 and could be used in topical formulations. [ABSTRACT FROM AUTHOR]

A proportion of somatic mutations in tumors create neoepitopes that can prime T cell responses that target the MHC I--neoepitope complexes on tumor cells, mediating tumor control or rejection. Despite the compelling centrality of neoepitopes to cancer immunity, we know remarkably little about what constitutes a neoepitope that can mediate tumor control in vivo and what distinguishes such a neoepitope from the vast majority of similar candidate neoepitopes that are inefficacious in vivo. Studies in mice as well as clinical trials have begun to reveal the unexpected paradoxes in this area. Because cancer neoepitopes straddle that ambiguous ground between self and non-self, some rules that are fundamental to immunology of frankly non-self antigens, such as viral or model antigens, do not appear to apply to neoepitopes. Because neoepitopes are so similar to self-epitopes, with only small changes that render them non-self, immune response to them is regulated at least partially the way immune response to self is regulated. Therefore, neoepitopes are viewed and understood here through the clarifying lens of negative thymic selection. Here, the emergent questions in the biology and clinical applications of neoepitopes are discussed critically and a mechanistic and testable framework that explains the complexity and translational potential of these wonderful antigens is proposed. [ABSTRACT FROM AUTHOR]

We isolated a high pathogenicity avian influenza (HPAI) virus from a common pochard (Aythya ferina) that was being attacked by a bird of prey in South Korea in December 2020. Genetic analyses indicated that the isolate was closely related to the clade 2.3.4.4b H5N8 HPAI viruses found in South Korea and Japan during the winter season of 2020–2021. The histopathological examination revealed multifocal necrotizing inflammation in the liver, kidney, and spleen. Viral antigens were detected in the liver, kidney, spleen, trachea, intestine, and pancreas, indicating the HPAI virus caused a systemic infection. The presence of immunoreactivity for the viral antigen was observed in the cells involved in multifocal necrotic inflammation. Notably, epitheliotropic-positive patterns were identified in the epithelial cells of the trachea, mucosal epithelium of the intestine, and ductular epithelium of the pancreas. These findings provide direct evidence supporting the possibility of HPAI transmission from infected waterfowl to predators. Detectado en el acto: Aislamiento y caracterización de un virus de la influenza aviar de alta patogenicidad del clado 2.3.4.4b H5N8 de un porrón común (Aythya ferina) atacado por un halcón peregrino (Falco peregrinus). Se aisló un virus de la influenza aviar (HPAI) de alta patogenicidad de un porrón común (Aythya ferina) que estaba siendo atacado por un ave rapaz en Corea del Sur en diciembre de 2020. Los análisis genéticos indicaron que el aislado estaba estrechamente relacionado con virus de influenza aviar de alta patogenicidad H5N8, clado 2.3.4.4 b encontrados en Corea del Sur y Japón durante la temporada de invierno de 2020–2021. El examen histopatológico reveló inflamación necrotizante multifocal en hígado, riñón y bazo. Se detectaron antígenos virales en el hígado, el riñón, el bazo, la tráquea, el intestino y el páncreas, lo que indica que este virus de alta patogenicidad causó una infección sistémica. Se observó la presencia de inmunorreactividad para el antígeno viral en las células involucradas en la inflamación necrótica multifocal. En particular, se identificaron patrones epiteliotrópicos positivos en las células epiteliales de la tráquea, el epitelio mucoso del intestino y el epitelio ductular del páncreas. Estos hallazgos proporcionan evidencia directa que respalda la posibilidad de transmisión de HPAI de aves acuáticas infectadas a especies depredadoras. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B is still a disease process that affects millions around the world. Serologies used to diagnose and follow the progression (or resolution) of the disease can be confusing for clinicians. Further, throughout years of treatment, there may be nuances in presentation that complicate management even further. In this short communication, we highlight six themes in response to treatment and outcomes, including complications. We have the unique perspective of following many patients over extended periods of time at our institution, which has brought these themes to life in order that they can be shared with other clinicians who may encounter similar situations. [ABSTRACT FROM AUTHOR]

Exosomes are small subtypes of extracellular vesicles (EVs) naturally released by different types of cells into their environment. Their physiological roles appear to be multiple, yet many aspects of their biological activities remain to be understood. These vesicles can transport and deliver a variety of cargoes and may serve as unconventional secretory vesicles. Thus, they play a crucial role as important vectors for intercellular communication and the maintenance of homeostasis. Exosome production and content can vary under several stresses or modifications in the cell microenvironment, influencing cellular responses and stimulating immunity. During infectious processes, exosomes are described as double-edged swords, displaying both beneficial and detrimental effects. Owing to their tractability, the analysis of EVs from multiple biofluids has become a booming tool for monitoring various pathologies, from infectious to cancerous origins. In this review, we present an overview of exosome features and discuss their particular and ambiguous functions in infectious contexts. We then focus on their properties as diagnostic or therapeutic tools. In this regard, we explore the capacity of exosomes to vectorize immunogenic viral antigens and their function in mounting adaptive immune responses. As exosomes provide interesting platforms for antigen presentation, we further review the available data on exosome engineering, which enables peptides of interest to be exposed at their surface. In the light of all these data, exosomes are emerging as promising avenues for vaccine strategies. [ABSTRACT FROM AUTHOR]

Antibiotic overprescribing is prevalent in pediatric emergency medicine, influenced by clinician–caregiver dynamics and diagnostic uncertainties, and poses substantial risks such as increasing antibacterial resistance, adverse drug reactions, and increased healthcare expenditures. While antimicrobial stewardship programs have proven effective in optimizing antibiotic use within inpatient healthcare settings, their implementation in pediatric emergency medicine presents specific challenges. Existing biomarkers like white blood cell count, C-reactive protein, procalcitonin, and presepsin have limitations in their ability to distinguish (serious) bacterial infections from other etiologies of fever. Furthermore, rapid antigen detection tests and guidelines aimed at guiding antibiotic prescriptions for children have not consistently reduced unnecessary antibiotic use. To improve antibiotic prescribing practices, potential strategies include the utilization of decision support tools, audit and feedback, establishing follow-up procedures, implementing safety netting systems, and delivering comprehensive training and supervision. Notably, host genome signatures have also gained attention for their potential to facilitate rapid and precise diagnoses of inflammatory syndromes. Standardized metrics are crucial for evaluating antimicrobial use within pediatric healthcare settings, enabling the establishment of benchmarks for assessing antibiotic utilization, quality enhancement initiatives, and research endeavors. [ABSTRACT FROM AUTHOR]

At the end of 2020, an outbreak of HPAI H5N8 was registered in captive African houbara bustards (Chlamydotis undulata) in the United Arab Emirates. In order to better understand the pathobiology of this viral infection in bustards, a comprehensive pathological characterization was performed. A total of six birds were selected for necropsy, histopathology, immunohistochemistry, RNAscope in situ hybridization and RT-qPCR and nanopore sequencing on formalin-fixed and paraffin-embedded (FFPE) tissue blocks. Gross lesions included mottled and/or hemorrhagic pancreas, spleen and liver and fibrinous deposits on air sacs and intestine. Necrotizing pancreatitis, splenitis and concurrent vasculitis, hepatitis and fibrino-heterophilic peritonitis were identified, microscopically. Viral antigens (nucleoprotein) and RNAs (matrix gene) were both detected within necro-inflammatory foci, parenchymal cells, stromal cells and endothelial cells of affected organs, including the myenteric plexus. Molecular analysis of FFPE blocks successfully detected HPAI H5N8, further confirming its involvement in the lesions observed. In conclusion, HPAI H5N8 in African houbara bustards results in hyperacute/acute forms exhibiting marked pantropism, endotheliotropism and neurotropism. In addition, our findings support the use of FFPE tissues for molecular studies of poorly characterized pathogens in exotic and endangered species, when availability of samples is limited. [ABSTRACT FROM AUTHOR]

There is currently a lot of interest in the construction of point-of-care devices stemming from paper-based origami biosensors. These devices demonstrate how paper's foldability permits the construction of sensitive, selective, user-friendly, intelligent, and maintainable analytical devices for the detection of several ailments. Herein, the first example of the electrochemical aptasensor-based polyvalent dengue viral antigen detection using the origami paper-folding method is presented. Coupling it with an aptamer leads to the development of a new notation known as OBAs, or origami-based aptasensor, that presents a multitude of advantages to the developed platform, such as assisting in safeguarding the sample from air-dust particles, providing confidentiality, and providing a closed chamber to the electrodes. In this paper, gold-decorated nanocomposites of zinc and graphene oxide (Au/ZnO/GO) were synthesized via the chemical method, and characterization was conducted by Scanning Electron Microscope, Transmission Electron Microscope, UV-Vis, and XRD which reveals the successful formation of nanocomposites, mainly helping to enhance the signal and specificity of the sensor by employing aptamers, since isolation and purification procedures are not required. The biosensor that is being demonstrated here is affordable, simple, and efficient. The reported biosensor is an OBA detection of polyvalent antigens of the dengue virus in human serum, presenting a good range from 0.0001 to 0.1 mg/mL with a limit of detection of 0.0001 mg/mL. The reported single-folding ori-aptasensor demonstrates exceptional sensitivity, specificity, and performance in human serum assays, and can also be used for the POC testing of various viral infections in remote areas and underdeveloped countries, as well as being potentially effective during outbreaks. Highlights: (1) First report on origami-based aptasensors for the detection of polyvalent antigens of DENV; (2) In-house construction of low-cost origami-based setup; (3) Gold-decorated zinc/graphene nanocomposite characterization was confirmed via FESEM/UV-Vis/FTIR; (4) Cross-reactivity of dengue-aptamer has been deduced; (5) Electrochemical validation was conducted through CV. [ABSTRACT FROM AUTHOR]

Although cells of the myeloid lineages, including tissue macrophages and conventional dendritic cells, were rapidly recognized, in addition to CD4+ T lymphocytes, as target cells of HIV-1, their specific roles in the pathophysiology of infection were initially largely neglected. However, numerous studies performed over the past decade, both in vitro in cell culture systems and in vivo in monkey and humanized mouse animal models, led to growing evidence that macrophages play important direct and indirect roles as HIV-1 target cells and in pathogenesis. It has been recently proposed that macrophages are likely involved in all stages of HIV-1 pathogenesis, including virus transmission and dissemination, but above all, in viral persistence through the establishment, together with latently infected CD4+ T cells, of virus reservoirs in many host tissues, the major obstacle to virus eradication in people living with HIV. Infected macrophages are indeed found, very often as multinucleated giant cells expressing viral antigens, in almost all lymphoid and non-lymphoid tissues of HIV-1-infected patients, where they can probably persist for long period of time. In addition, macrophages also likely participate, directly as HIV-1 targets or indirectly as key regulators of innate immunity and inflammation, in the chronic inflammation and associated clinical disorders observed in people living with HIV, even in patients receiving effective antiretroviral therapy. The main objective of this review is therefore to summarize the recent findings, and also to revisit older data, regarding the critical functions of tissue macrophages in the pathophysiology of HIV-1 infection, both as major HIV-1-infected target cells likely found in almost all tissues, as well as regulators of innate immunity and inflammation during the different stages of HIV-1 pathogenesis. [ABSTRACT FROM AUTHOR]

Background While the modes of transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are well studied, the risk of transmission in various group settings or activities is less clear. This living scoping review aims to summarize the risk factors of coronavirus disease 2019 (COVID-19) spread in common group activities (e.g. social gatherings) or settings (e.g. schools, hospitals, shared workplaces) to understand the drivers of transmission and to inform a risk assessment profile tool for use of rapid antigen detection tests. Methods We systematically searched electronic databases, MEDLINE and Embase, from January 2019 until February 2022. We included studies that evaluated the risk of SARS-CoV-2 transmission in activities and settings, deemed strategically important to government departments in Ireland, provided by the Department of Health (Ireland) Expert Advisory Group on Rapid Testing. Results After screening 14 052 records, data from 139 studies were narratively synthesized. The risk was consistently reported as 'high' for large social events (e.g. weddings) and indoor sports, working in healthcare settings and shared workplaces, working/living in residential settings and travelling via public transportation. Most studies were from healthcare settings, with common risk factors including close contact with COVID-19 cases, working in high-risk departments and inappropriate use of personal protective equipment. For other settings and activities, lack of infection prevention and control practices reportedly contributed to infection transmission. Conclusion The heterogeneity across studies and lack of direct information on dominant variants, preventive measures, vaccination coverage necessitates further research on transmission risk within group activities to inform infection prevention and control measures. [ABSTRACT FROM AUTHOR]

Borna disease (BD) associated with a peracute bacterial septicaemia with Escherichia coli was diagnosed in an adult female, naturally infected, free-ranging Eurasian beaver of the subspecies Castor fiber albicus , clinically characterized by weight loss, depression, weakness and gurgled peristaltic sounds. The beaver was euthanized humanely. Necropsy and light microscopy revealed a non-purulent meningoencephalitis with typical mononuclear perivascular cuffs and parenchymal infiltrates. The diagnosis of BD was confirmed by detection of viral antigen and RNA by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). The PCR product was sequenced and cluster analysis revealed a close relationship between endemic clusters in Saxony-Anhalt. This is the first report of naturally occurring BD in a free-ranging Eurasian beaver. [ABSTRACT FROM AUTHOR]

CD4+ T cells play a critical role in the pathogenesis of viral diseases, which are activated by the internal metabolic pathways encountering with viral antigens. Glutaminolysis converts glutamine into tricarboxylic acid (TCA) circulating metabolites by α-ketoglutaric acid, which is essential for the proliferation and differentiation of CD4+ T cells and plays a central role in providing the energy and structural components needed for viral replication after the virus hijacks the host cell. Changes in glutaminolysis in CD4+ T cells are accompanied by changes in the viral status of the host cell due to competition for glutamine between immune cells and host cells. More recently, attempts have been made to treat tumours, autoimmune diseases, and viral diseases by altering the breakdown of glutamine in T cells. In this review, we will discuss the current knowledge of glutaminolysis in the CD4+ T cell subsets from viral diseases, not only increasing our understanding of immunometabolism but also providing a new perspective for therapeutic target in viral diseases. [ABSTRACT FROM AUTHOR]

Nucleic acid delivery through extracellular vesicles (EVs) is a well-preserved evolutionary mechanism in all life kingdoms including eukaryotes, prokaryotes, and plants. EVs naturally allow horizontal transfer of native as well as exogenous functional mRNAs, which once incorporated in EVs are protected from enzymatic degradation. This observation has prompted researchers to investigate whether EVs from different sources, including plants, could be used for vaccine delivery. Several studies using human or bacterial EVs expressing mRNA or recombinant SARS-CoV-2 proteins showed induction of a humoral and cell mediated immune response. Moreover, EV-based vaccines presenting the natural configuration of viral antigens have demonstrated advantages in conferring long-lasting immunization and lower toxicity than synthetic nanoparticles. Edible plant-derived EVs were shown to be an alternative to human EVs for vaccine delivery, especially via oral administration. EVs obtained from orange juice (oEVs) loaded with SARS-CoV-2 mRNAs protected their cargo from enzymatic degradation, were stable at room temperature for one year, and were able to trigger a SARS-CoV-2 immune response in mice. Lyophilized oEVs containing the S1 mRNA administered to rats via gavage induced a specific humoral immune response with generation of blocking antibodies, including IgA and Th1 lymphocyte activation. In conclusion, mRNA-containing oEVs could be used for developing new oral vaccines due to optimal mucosal absorption, resistance to stress conditions, and ability to stimulate a humoral and cellular immune response. [ABSTRACT FROM AUTHOR]

South Korea has experienced outbreaks of foot-and-mouth disease (FMD) of serotypes O and A, leading to nationwide vaccination with a bivalent vaccine. Since the FMD virus (FMDV) Asia1 group-V genotype occurred in North Korea in 2007, an Asia1/MOG/05 vaccine strain belonging to the Asia1 group-V genotype was developed using a genetic recombination method (Asia1/MOG/05-R). This study aimed to evaluate the antigen productivity and viral inactivation kinetics of Asia1/MOG/05-R to assess its commercial viability. The antigen yield of Asia1/MOG/05-R produced in flasks and bioreactors was approximately 4.0 μg/mL. Binary ethylenimine (BEI) inactivation kinetics of Asia1/MOG/05-R showed that 2 mM and 1.0 mM BEI treatment at 26 °C and 37 °C, respectively, resulted in a virus titer <10−7 TCID50/mL within 24 h, meeting the inactivation kinetics criteria. During incubation at 26 °C and 37 °C, 10% antigen loss occurred, but not due to BEI treatment. When pigs were inoculated twice with the Asia1/MOG/05-R antigen, the virus neutralization titer increased to approximately 1:1000; therefore, it can sufficiently protect against Asia1/MOG/05-R and Asia1 Shamir viruses. The Asia1/MOG/05-R will be useful as a vaccine strain for domestic antigen banks. [ABSTRACT FROM AUTHOR]

The Interferon Stimulated Gene 15 (ISG15), a unique Ubiquitin-like (Ubl) modifier exclusive to vertebrates, plays a crucial role in the immune system. Primarily induced by interferon (IFN) type I, ISG15 functions through diverse mechanisms: (i) covalent protein modification (ISGylation); (ii) non-covalent intracellular action; and (iii) exerting extracellular cytokine activity. These various roles highlight its versatility in influencing numerous cellular pathways, encompassing DNA damage response, autophagy, antiviral response, and cancer-related processes, among others. The well-established antiviral effects of ISGylation contrast with its intriguing dual role in cancer, exhibiting both suppressive and promoting effects depending on the tumour type. The multifaceted functions of ISG15 extend beyond intracellular processes to extracellular cytokine signalling, influencing immune response, chemotaxis, and anti-tumour effects. Moreover, ISG15 emerges as a promising adjuvant in vaccine development, enhancing immune responses against viral antigens and demonstrating efficacy in cancer models. As a therapeutic target in cancer treatment, ISG15 exhibits a double-edged nature, promoting or suppressing oncogenesis depending on the tumour context. This review aims to contribute to future studies exploring the role of ISG15 in immune modulation and cancer therapy, potentially paving the way for the development of novel therapeutic interventions, vaccine development, and precision medicine. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to identify the pathogen spectrum of community acquired pneumonia in people living with HIV (PLWH), and to compare it with a matched HIV negative group in order to reassess therapeutic strategies for PLWH. Methods: Seventy-three (n = 73) PLWH (median CD4 3–6 months before CAP: 515/µl; SD 309) with community acquired pneumonia (CAP) were matched with 218 HIV-negative CAP controls in a prospective study design. Pathogen identifications used blood culture, samples from the upper and lower respiratory tract (culture and multiplex PCR) and urinary pneumococcal and legionella antigen test. Results: Although the vaccination rate among PLWH with CAP was significantly higher (pneumococcal vaccination: 27.4 vs. 8.3%, p < 0.001; influenza vaccination: 34.2 vs. 17.4%, p = 0.009), pneumococci were found most frequently as pathogen among both PLWH (n = 19/21.3%) and controls (n = 34/17.2%; p = 0.410), followed by Haemophilus influenzae (PLWH, n = 12/13.5%, vs. controls, n = 25 / 12.6%; p = 0.850). Staphylococcus aureus was found equally in 20.2 and 19.2% in PLWH and controls, but infection or colonization could not be distinguished. Mortality during 6-month follow-up was significantly higher for PLWH (5/73, or 6.8%) versus controls (3/218, or 1.4%), however with lower case numbers than previously reported. Typical HIV-associated pathogens such as Pneumocystis jirovecii were found only exceptionally. Conclusions: Our study underscores the persistent clinical burden of CAP for PLWH. From pathogen perspective, empirical antibiotic treatment for CAP in PLWH on antiretroviral therapy should cover pneumococci and Haemophilus influenzae and may be adopted from valid common recommendations. [ABSTRACT FROM AUTHOR]

Respiratory infections are quite challenging due to their complexity in ailments and composition of viral genetic material and their rate of proliferation. In particular, the eradication of viral illness is still a concern, irrespective of advancements in prevention and remedial procedures. The nature of the viral particle with the possibility of rapid transmission is prone to attach on the deposited surface for days together. This antigen expulses due to sneezing or coughing resulted in multiphase turbulent flow, contaminates the surroundings and is carried away by simple touch or inhalation and find newer hosts for instance, SARSCoV-2 aerosols remain viable for about an hour leading to infection. The present review focuses on the remedial aspects of respiratory infections through a knowledge-based approach towards nanosystems. The complete understanding of standard antiviral drugs and the remodelling of these drugs through nanosystems still is the need of the hour. The genetic material and epidemiology of viral antigen, help in redefining standard drugs along with nanocarriers to achieve more feasible and hour-based approach. The main goal of this review is to elaborate on the repurposing of existing standard antiviral drugs and ways to accelerate their mode of action to promote a feasible and hour-based approach. The consolidated three-dimensional approaches aimed at sustained, targeted and optimized levels of drug concentration in the circulating system along with bioactive nanocarriers which could effectively pass the cell membrane were reported. The platforms for nanomaterial evolution depend on nature of source, size, structure, and their unique functionalities (Stable, speedy, and long-lasting recovery procedure). However, the research activities and literature on coronavirus have been overwhelming but the information on the sustainability of nanotherapy in SARS-CoV-2 is still in the developmental stage. Hereby, the clinical aspects of SARS-CoV-2 and the eradication strategy developed for antiviral infections through nanotechnology will pave the way ahead for treating upcoming new variants or other pandemics. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are small membrane-enclosed structures that have gained much attention from researchers across varying scientific fields in the past few decades. Cells secrete diverse types of EVs into the extracellular milieu which include exosomes, microvesicles, and apoptotic bodies. These EVs play a crucial role in facilitating intracellular communication via the transport of proteins, lipids, DNA, rRNA, and miRNAs. It is well known that a number of viruses hijack several cellular pathways involved in EV biogenesis to aid in their replication, assembly, and egress. On the other hand, EVs can also trigger host antiviral immune responses by carrying immunomodulatory molecules and viral antigens on their surface. Owing to this intricate relationship between EVs and viruses, intriguing studies have identified various EV-mediated viral infections and interrogated how EVs can alter overall viral spread and longevity. This review provides a comprehensive overview on the EV-virus relationship, and details various modes of EV-mediated viral spread in the context of clinically relevant enveloped and non-enveloped viruses. [ABSTRACT FROM AUTHOR]

Background: Biological sex plays an integral role in the immune response to various pathogens. The underlying basis for these sex differences is still not well defined. Here, we show that Coxsackievirus B3 (CVB3) induces a viral-specific CD4+ T cell response that can protect female mice from mortality. Methods: We inoculated C57BL/6 Ifnar-/- mice with CVB3. We investigated the T cell response in the spleen and mesenteric lymph nodes in male and female mice following infection. Results: We found that CVB3 can induce expansion of CD62Llo CD4+ T cells in the mesenteric lymph node and spleen of female but not male mice as early as 5 days post-inoculation, indicative of activation. Using a recombinant CVB3 virus expressing a model CD4+ T cell epitope, we found that this response is due to viral antigen and not bystander activation. Finally, the depletion of CD4+ T cells before infection increased mortality in female mice, indicating that CD4+ T cells play a protective role against CVB3 in our model. Conclusions: Overall, these data demonstrated that CVB3 can induce an early CD4 response in female but not male mice and further emphasize how sex differences in immune responses to pathogens affect disease. [ABSTRACT FROM AUTHOR]

We evaluated the diagnostic performance of the STANDARD i-Q COVID-19 Ag Test, which was developed to detect viral antigens, using nasal and oral swabs. Sixty positive and 100 negative samples were analyzed. We determined the distribution of the Ct values according to the day of sample collection after symptom onset, the diagnostic performance of the total samples and subgroups separated by Ct value or time of sample collection, and the Ct value at which maximal accuracy was expected. No differences were observed in Ct values, except for the samples obtained on the day of symptom onset. The diagnostic sensitivity and specificity of the oral swabs were 75.0 and 100.0%, respectively, whereas those of the nasal swabs were 85.0 and 98.0%, respectively. The sensitivity was higher in samples with a high viral load collected earlier than those collected later, although the difference was not significant. False-negative results were confirmed in all samples with a Ct value ≥ 30.0. These results indicate that tests using oral and nasal swabs are helpful for diagnosing acute symptomatic cases with suspected high viral loads. Our tests exhibited relatively low sensitivity but high specificity rates, indicating the need to assess negative antigen test results. [ABSTRACT FROM AUTHOR]

Nowadays, the population is still struggling with a post-COVID19 syndrome known as long COVID, including a broad spectrum of neurological problems. There is an urgent need for a better understanding and exploration of the mechanisms of coronavirus neurotropism. For this purpose, the neurotropic strain of mouse hepatitis virus (MHV-JHM) originating from the beta-coronavirus genus, the same as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been used. The role of the cytoskeleton during virus replication in neurons in vitro was determined to understand the mechanisms of MHV-JHM neuroinfection. We have described for the first time the changes of actin filaments during MHV-JHM infection. We also observed productive replication of MHV-JHM in neurons during 168 h p.i. and syncytial cytopathic effect. We discovered that the MHV-JHM strain modulated neuronal cytoskeleton during infection, which were manifested by: (i) condensation of actin filaments in the cortical layer of the cytoplasm, (ii) formation of microtubule cisternae structures containing viral antigen targeting viral replication site (iii) formation of tunneling nanotubes used by MHV-JHM for intercellular transport. Additionally, we demonstrated that the use of cytoskeletal inhibitors have reduced virus replication in neurons, especially noscapine and nocodazole, the microtubule shortening factors. [ABSTRACT FROM AUTHOR]

Background: A number of laboratory data and clinical studies have shown that probiotic bacteria may be beneficial in respiratory viral diseases. We investigated the role of probiotics in coronavirus disease-19 (COVID -19), post-disease symptoms, and humoral immune responses to viral antigens. Methods: This was a randomized, double-blind, placebo-controlled, prospective, multicenter study. We included symptomatic patients aged 18–65 years without risk of severe disease, and positive antigen/PCR test for SARS-CoV-2. Patients received (Bifidobacterium (B.) lactis BI040, B. longum BL020, Lactobacillus (L) rhamnosus LR110, L. casei LC130, L. acidophilus LA120, 5 billion CFU total) or placebo 1 capsule a day for 28 days and recorded symptoms. Three months later patients completed Post-COVID-19 Questionnaire (PCQ-19). On days 0–5 and 28–35, blood was sampled for IgG to nucleocapsid protein (NCP) and receptor binding domain (RBD)/spike 1 (S1) protein. The primary outcome measure was a patient global symptom score on day 10 of observation. The difference between groups was assessed using the Mann–Whitney U test. Results: Seventy-three patients were assessed for clinical endpoints and 44 patients were evaluated for antibody production. At day 10, the median global symptom score (interquartile range) was lower in the probiotic group (0.0 (0.0–2.0) vs. 2.0 (1.0–5.0), P < 0.05). The probiotic group had a shorter duration of fatigue and anxiety after COVID -19 (P < 0.05) and a greater change in IgG concentration on RBD/S1 (225.9 vs. 105.6 binding antibody units/mL, P < 0.05). Conclusions: Use of probiotics alleviates acute and post-disease symptoms, and improves humoral immune response to viral antigens. Trial registration: Registered at clinicaltrials.gov as NCT04907877, June 1, 2021. [ABSTRACT FROM AUTHOR]

Zoonotic transmission of H5N1 highly pathogenic avian influenza virus (HPAIV) into the human population is an increasing global threat. The recent 2022 HPAIV outbreak significantly highlighted this possibility, increasing concern in the general population. The clinical outcomes of H5N1 influenza virus exposure can be determined by an individual’s primary influenza virus infection (imprinting) or vaccination status. Immunological imprinting with Group 1 - (H1N1, H2N2, and H2N3) increases survival rates following H5N1 viral infection compared to Group 2 - (H3N2) imprinted individuals. Vaccination against H5N1 influenza viruses can offer protection to at-risk populations; however, stockpiled inactivated H5N1 influenza vaccines are not readily available to the public. We hypothesize that the immunological response to vaccination and subsequent clinical outcome following H5N1 influenza virus infection is correlated with the immunological imprinting status of an individual. To test this hypothesis, our lab established a ferret pre-immune model of disease. Naïve ferrets were intranasally inoculated with seasonal influenza viruses and allowed to recover for 84  days prior to H5N1 virus infection. Ferrets imprinted following H1N1 and H2N3 virus infections were completely protected against lethal H5N1 influenza virus challenge (100% survival), with few to no clinical symptoms. In comparison, H3N2 influenza virus)imprinted ferrets had severe clinical symptoms, delayed disease progression, and a sublethal phenotype (40% mortality). Consecutive infections with H1N1 influenza viruses followed by an H3N2 influenza virus infection did not abrogate the immune protection induced by the original H1N1 influenza virus infection. In addition, ferrets consecutively infected with H1N1 and H2N3 viruses had no clinical symptoms or weight loss. H3N2 pre-immune ferrets were vaccinated with a broadly reactive H5 HA-based or H1 NA-based vaccine (Hu-CO 2). These ferrets were protected against H5N1 influenza virus challenge, whereas ferrets vaccinated with the H1N1 wild-type CA/09 rHA vaccine had similar phenotypes as non-vaccinated H3N2-imprinted ferrets with 40% survival. Overall, Group 2 imprinted ferrets, which were vaccinated with heterologous Group 1 HA vaccines, had redirected immune responses to Group 1 influenza viral antigens and rescued a sublethal phenotype to complete protection. [ABSTRACT FROM AUTHOR]

The introduction of three single nucleotide mutations into the genome of the virulent RVFV ZH548 strain allows for the rescue of a fully attenuated virus in mice (ZH548-rA2). These mutations are located in the viral genes encoding the RdRp and the non-structural protein NSs. This paper shows the results obtained after the subcutaneous inoculation of ZH548-rA2 in adult sheep and the subsequent challenge with the parental virus (ZH548-rC1). Inoculation with the ZH548-rA2 virus caused no detectable clinical or pathological effect in sheep, whereas inoculation of the parental rC1 virus caused lesions compatible with viral infection characterised by the presence of scattered hepatic necrosis. Viral infection was confirmed via immunohistochemistry, with hepatocytes within the necrotic foci appearing as the main cells immunolabelled against viral antigen. Furthermore, the inoculation of sheep with the rA2 virus prevented the liver damage expected after rC1 virus inoculation, suggesting a protective efficacy in sheep which correlated with the induction of both humoral and cell-mediated immune responses. [ABSTRACT FROM AUTHOR]

African swine fever (ASF) is a highly contagious disease caused by African swine fever virus (ASFV), affecting domestic and wild boars. The polyprotein pp220 of ASFV is responsible for producing the major structural proteins p150, p37, p14, p34, and p5 via proteolytic processing. The p34 protein is the main component of the ASFV core shell. However, the immunologic properties of the p34 protein in vitro and in vivo remain unclear. The results showed that the recombinant p34 protein expressed in prokaryotes and eukaryotes could react with convalescent swine sera to ASFV, suggesting that p34 is an immunogenic protein. Significantly, anti-p34 antibodies were found to inhibit the replication of ASFV in target cells. Furthermore, rabbits immunized with the recombinant C-strain of classical swine fever virus containing p34 produced both anti-p34 humoral and cellular immune responses. In addition, the p34 protein could induce a cell-mediated immune response, and a T-cell epitope on the p34 protein was identified using immunoinformatics and enzyme-linked immunospot (ELIspot) assay. Our study demonstrates that the p34 protein is a novel antigen of ASFV with protective potential. [ABSTRACT FROM AUTHOR]

Following the conclusion of the COVID-19 pandemic, the persistent genetic variability in the virus and its ongoing circulation within the global population necessitate the enhancement of existing preventive vaccines and the development of novel ones. A while back, we engineered an orally administered probiotic-based vaccine, L3-SARS, by integrating a gene fragment that encodes the spike protein S of the SARS-CoV-2 virus into the genome of the probiotic strain E. faecium L3, inducing the expression of viral antigen on the surface of bacteria. Previous studies demonstrated the efficacy of this vaccine candidate in providing protection against the virus in Syrian hamsters. In this present study, utilizing laboratory mice, we assess the immune response subsequent to immunization via the gastrointestinal mucosa and discuss its potential as an initial phase in a two-stage vaccination strategy. Our findings indicate that the oral administration of L3-SARS elicits an adaptive immune response in mice. Pre-immunization with L3-SARS enhances and prolongs the humoral immune response following a single subcutaneous immunization with a recombinant S-protein analogous to the S-insert of the coronavirus in Enterococcus faecium L3. [ABSTRACT FROM AUTHOR]

The aim of this work is to analyze the viral titers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory syncytial virus (RSV) at the anterior nasal site (ANS) and nasopharyngeal site (NS), evaluate their virological dynamics, and validate the usefulness of a newly developed two-antigen-detecting rapid antigen diagnostic test (Ag-RDT) that simultaneously detects SARS-CoV-2 and RSV using clinical specimens. This study included 195 asymptomatic to severely ill patients. Overall, 668 specimens were collected simultaneously from the ANS and NS. The cycle threshold (Ct) values calculated from real-time polymerase chain reaction were used to analyze temporal changes in viral load and evaluate the sensitivity and specificity of the Ag-RDT. The mean Ct values for SARS-CoV-2-positive, ANS, and NS specimens were 28.8, 28.9, and 28.7, respectively. The mean Ct values for RSV-positive, ANS, and NS specimens were 28.7, 28.8, and 28.6, respectively. SARS-CoV-2 and RSV showed the same trend in viral load, although the viral load of NS was higher than that of ANS. The sensitivity and specificity of the newly developed Ag-RDT were excellent in specimens collected up to 10 days after the onset of SARS-CoV-2 infection and up to 6 days after the onset of RSV infection. [ABSTRACT FROM AUTHOR]

Background and Aim: Infection with Epstein-Barr virus (EBV) ranks as one of the most substantial risk factors associated with Glioblastoma multiforme (GBM). At the core of this intricate relationship lies the EBV nuclear antigen-1 (EBNA1) protein, a central figure with a remarkable ability to regulate the expression of both cellular and viral genes. This research delves into the impact of EBNA1 on the expression patterns of four cellular genes - MDMX, MDM2, MYC, and BIRC5 in the U87MG cell line. Materials and Methods: We divided U87MG cells into two distinct groups. The first group involved cells that were transfected with a plasmid containing the EBNA1 gene, while the second group consisted of cells that were transfected with a control plasmid. To evaluate the transcriptional activity of MDMX, MDM2, MYC, and BIRC5 genes in both sets of cells, we employed a real-time PCR technique. Any observed differences were considered statistically significant if the associated Pvalues were less than 0.05. Results: Our findings demonstrated a substantial three-fold increase in the expression of the MDMX gene when U87MG cells were transfected with EBNA1 plasmid (P=0.02). Although the cells transfected with EBNA1 plasmid displayed great elevations in the expression levels of MDM2, MYC, and BIRC5 genes, these alterations were not statistically significant. Conclusion: The outcomes of this investigation have unveiled that EBNA1 has the ability to trigger the expression of four crucial cellular genes, which wield substantial influence in the genesis of GBM within glioblastoma astrocytoma cells. This underscores the potential impact of EBNA1 on the evolution of GBM, particularly in individuals harboring EBV. [ABSTRACT FROM AUTHOR]

Background and Aim: Co-infection of HBV and HDV leads to more severe hepatitis, with a higher risk of acute liver failure and hepatocellular carcinoma (HCC). This study aimed to assess the prevalence of HDV in HBsAg-positive patients in Khorramabad, which has not been previously evaluated. Materials and Methods: A total of 200 patients who tested positive for HBsAg were included in this study. Venous blood samples were collected in EDTA-free tubes. An ELISA test was performed to detect antibodies against HDV, and positive samples were further confirmed using RT-PCR. Population data were analyzed using SPSS software, and a P value ≤0.05 was considered statistically significant for all tests. Results: Out of the total participants, there were 119 (59.5%) men and 81 (40.5%) women. The age of the patients varied from 5 to 89 years, with an average age of 49.66 years. The HDV ELISA test was performed on HBsAg-positive individuals, yielding positive results for 37 (18.5%) patients. Additionally, 10 (5%) patients showed borderline infection. The HDV RTPCR results indicated that 42 (21%) individuals tested positive. The prevalence of HDV showed a statistically significant difference between urban and rural areas with respect to molecular RT-PCR testing (P=0.032). Additionally, women, married individuals, and drug addicts were found to be at a higher risk of HDV infection. Conclusion: There is a high prevalence of HDV infection among patients who test positive for HBsAg in Khorramabad. Therefore, assessing the prevalence of HDV in HBsAg-positive patients can aid in ensuring timely diagnosis and appropriate treatment for these individuals. [ABSTRACT FROM AUTHOR]

There is a strong association between the distribution of Hepatitis B virus (HBV) carriers and the incidence of hepatocellular carcinoma (HCC). About 60% of HCC in Japan is caused by viral hepatitis. Ten to 15 percent of hepatitis virus-related HCCs derive from HBV. Recently, antiviral therapy against HBV has developed, and interferon therapy and nucleos(t)ide analogues (NAs) are currently the standard of care. NAs exhibit antiviral activity by inhibiting DNA polymerase and suppressing HBV replication. NAs are highly effective in suppressing HBV-DNA and improving alanine aminotransferase. The long-term treatment goal for chronic hepatitis B is HB surface antigen (HBsAg) loss. However, the number of patients who achieve HBsAg loss by NA (i.e., functional cure) is low and there have been cases of HCC incidence during (or after) NA therapy. In this article, we review the efficacy of NA therapy in suppressing HBV-derived carcinogenesis. [ABSTRACT FROM AUTHOR]

A recent study published in the National Science Review discusses the development of virus-like nanoparticle vaccines for inducing long-lasting immunity against infectious diseases. The study focuses on the engineering of multifunctional viromimetic polymer nanoparticle vaccines (VPNVax) against SARS-CoV-2. The researchers used a self-assembling polymeric nanoparticle platform and conjugated receptor-binding domain (RBD) proteins to the surface of the nanoparticle. The study found that the VPNVax platform with optimal antigen valency elicited the highest antibody responses and demonstrated longer retention in lymph nodes, indicating its potential as an effective vaccine platform. [Extracted from the article]

Canine distemper virus (CDV) is a major global pathogen of dogs affecting multiple organ systems of the body and causing the characteristic malady with prominent neurological manifestation. Natural CDV infections with typical clinical symptoms in domestic cats are not yet reported in Kerala, India, even though a few reports on the occurrence of fatal canine distemper in large felids exist. The present study reports a documented preliminary report of the natural canine distemper virus infection in a domestic cat from Kerala, India, with typical neurological manifestations. An unvaccinated adult female domestic cat was presented to the University Veterinary Hospital with the acute onset of neurological signs, viz. typical continuous myoclonus like in a CDV-infected dog and tonic-clonic seizures in between the short intervals of time. The rapid immunochromatography revealed the presence of canine distemper viral antigens on ocular, nasal and faecal samples, and the hemogram revealed thrombocytopenia and severe leukocytosis with granulocytosis, lymphocytosis and monocytosis. The animal responded well to the symptomatic therapy for viral encephalitis and recovered within 24 h to apparent normalcy, except for the myoclonus. The recurrence of acute encephalitic symptoms was reported after 45 days, and the animal died due to uncontrolled seizures by day 90, as the owner was unwilling to provide further veterinary aid for the animal. This case indicates the need for screening the cats with neurological signs for CD and further molecular characterisation of the strains involved. [ABSTRACT FROM AUTHOR]

Simple Summary: The translational gap poses a challenge for therapeutic cancer vaccine development, including HPV-specific therapeutic vaccines. The aim of this study was to evaluate a new human ex vivo PBMC assay that mimics how viral-vectored vaccines induce T-cell responses in vivo. In brief, PBMCs are taken through rounds of stimulation by co-culturing with syngeneic DCs, which have been previously matured and transduced with the viral-vector-based vaccine. We evaluated the assay using a novel HPV16-specific therapeutic vaccine in healthy human donors with pre-existing T-cell responses against HPV16 to simulate a therapeutic setting. The pre-existing T-cell responses were effectively boosted to a larger extent by vaccine-transduced DCs than by peptide-pulsing, and the T cells could specifically recognize and kill HPV16+ human cancer cells. Additionally, this study supports the use of nucleic-acid-based vaccines for optimal cancer recognition and indicates an immunological advantage of targeting the HPV E1 gene. Persistent human papillomavirus (HPV) infection is responsible for practically all cervical and a high proportion of anogenital and oropharyngeal cancers. Therapeutic HPV vaccines in clinical development show great promise in improving outcomes for patients who mount an anti-HPV T-cell response; however, far from all patients elicit a sufficient immunological response. This demonstrates a translational gap between animal models and human patients. Here, we investigated the potential of a new assay consisting of co-culturing vaccine-transduced dendritic cells (DCs) with syngeneic, healthy, human peripheral blood mononuclear cells (PBMCs) to mimic a human in vivo immunization. This new promising human ex vivo PBMC assay was evaluated using an innovative therapeutic adenovirus (Adv)-based HPV vaccine encoding the E1, E2, E6, and E7 HPV16 genes. This new method allowed us to show that vaccine-transduced DCs yielded functional effector T cells and unveiled information on immunohierarchy, showing E1-specific T-cell immunodominance over time. We suggest that this assay can be a valuable translational tool to complement the known animal models, not only for HPV therapeutic vaccines, and supports the use of E1 as an immunotherapeutic target. Nevertheless, the findings reported here need to be validated in a larger number of donors and preferably in patient samples. [ABSTRACT FROM AUTHOR]

Background: Porcine epidemic diarrhea (PED), caused by PED virus (PEDV), is a severe enteric disease burdening the global swine industry in recent years. Especially, the mortality of PED in neonatal piglets approaches 100%. Maternal antibodies in milk, particularly immunoglobulin A (IgA) antibodies, are of great importance for protection neonatal suckling piglets against PEDV infection as passive lactogenic immunity. Therefore, appropriate detection methods are required for detecting PEDV IgA antibodies in milk. In the current study, we prepared monoclonal antibodies (mAbs) against PEDV spike (S) glycoprotein. An enzyme-linked immunosorbent assay (ELISA) was subsequently developed based on PEDV antigen capture by a specific anti-S mAb. Results: The developed ELISA showed high sensitivity (the maximum dilution of milk samples up to 1:1280) and repeatability (coefficient of variation values < 10%) in detecting PEDV IgA antibody positive and negative milk samples. More importantly, the developed ELISA showed a high coincidence rate with a commercial ELISA kit for PEDV IgA antibody detection in clinical milk samples. Conclusions: The developed ELISA in the current study is applicable for PEDV IgA antibody detection in milk samples, which is beneficial for evaluating vaccination efficacies and neonate immune status against the virus. [ABSTRACT FROM AUTHOR]

Introduction: There are limited data on the efficacy of baloxavir marboxil (baloxavir) versus oseltamivir in Chinese patients with influenza A. Methods: This study is an observational real-world investigation encompassing 246 patients (baloxavir, n = 147; oseltamivir, n = 99) confirmed positive for influenza A. The choice between baloxavir and oseltamivir antiviral treatments was determined collaboratively by the clinician and the patient. A thorough comparative analysis was undertaken between the two groups, examining parameters such as the duration of fever and symptoms, viral load dynamics, lymphocyte changes, and enhancements in health-related quality of life (QoL). Results: No significant differences were observed in demographic data between the two groups. The duration of fever was significantly shorter in the baloxavir group (P < 0.001). However, the duration of symptoms was not significant different (P = 0.167). Multivariable Cox analysis showed the independent factors affecting duration of fever were baloxavir treatment (HR = 2.033, P < 0.001), fever on day 1 (HR = 0.741, P = 0.010) and CRP level (HR = 1.009, P = 0.039). Moreover, sex (HR= 0.660, P = 0.019) and monocyte count (HR = 1.355, P = 0.018) were independent factors affecting the duration of symptoms. No significant difference in change of health-related quality of life (P > 0.05), positive rate of viral antigen on day 3 (P = 0.477) between the two groups. Remarkably, a mutation was observed in one case on the third-day after baloxavir treatment compared with first-day, from cysteine to serine at position 384 of the PA subunit. Conclusion: In the clinical setting, baloxavir demonstrated comparable clinical benefits to oseltamivir, establishing its efficacy as an effective antiviral therapy for Chinese patients with influenza. [ABSTRACT FROM AUTHOR]

Several viruses including human herpes viruses (HHVs), human polyomavirus JCV, and human papilloma virus (HPV) have been implicated in brain cancer, albeit inconsistently. Since human leukocyte antigen (HLA) is centrally involved in the human immune response to viruses and has been implicated in brain cancer, we evaluated in silico the immunogenicity between 69 Class I HLA alleles with epitopes of proteins of 9 HHVs, JCV, and HPV with respect to a population-based HLA-brain cancer profile. We found that immunogenicity varied widely across HLA alleles with HLA-C alleles exhibiting the highest immunogenicity, and that immunogenicity scores were negatively associated with the population-based HLA-brain cancer profile, particularly for JCV, HHV6A, HHV5, HHV3, HHV8, and HHV7. Consistent with the role of HLA in foreign antigen elimination, the findings suggest that viruses with proteins of high HLA immunogenicity are eliminated more effectively and, consequently, less likely to cause brain cancer; conversely, the absence of highly immunogenic HLA may allow the viral antigens to persist, contributing to cancer. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the worldwide COVID-19 pandemic. Animal models are extremely helpful for testing vaccines and therapeutics and for dissecting the viral and host factors that contribute to disease severity and transmissibility. Here, we report the assessment and comparison of intranasal and small particle (~3 µm) aerosol SARS-CoV-2 exposure in ferrets. The primary endpoints for analysis were clinical signs of disease, recovery of the virus in the upper respiratory tract, and the severity of damage within the respiratory tract. This work demonstrated that ferrets were productively infected with SARS-CoV-2 following either intranasal or small particle aerosol exposure. SARS-CoV-2 infection of ferrets resulted in an asymptomatic disease course following either intranasal or small particle aerosol exposure, with no clinical signs, significant weight loss, or fever. In both aerosol and intranasal ferret models, SARS-CoV-2 replication, viral genomes, and viral antigens were detected within the upper respiratory tract, with little to no viral material detected in the lungs. The ferrets exhibited a specific IgG immune response to the SARS-CoV-2 full spike protein. Mild pathological findings included inflammation, necrosis, and edema within nasal turbinates, which correlated to positive immunohistochemical staining for the SARS-CoV-2 virus. Environmental sampling was performed following intranasal exposure of ferrets, and SARS-CoV-2 genomic material was detected on the feeders and nesting areas from days 2–10 post-exposure. We conclude that both intranasal and small particle aerosol ferret models displayed measurable parameters that could be utilized for future studies, including transmission studies and testing SARS-CoV-2 vaccines and therapeutics. [ABSTRACT FROM AUTHOR]

Objectives: The present study was conducted to assess the pattern of HBV Core/Pre-Core mutations and HBV genotype in Iraqi patients with chronic hepatitis B virus (HBV) infection. Methods: In the current cross-sectional study in an Iraqi province, we evaluated 134 patients diagnosed with HBV hepatitis. We used PCR and, subsequently, Sanger sequencing to assess HBV Core/Pre-Core mutations. Sanger sequencing reads were further used for phylogenetic analysis and multiple sequence alignment. A phylogenetic tree was generated according to the neighbor-joining method. Results: The current study revealed that 58 (45%) of the patients were male, and 72 (55%) of them were female. The mean age of the patients was 36 ± 12.7 years, and the mean duration of infection was 5.2 ± 4.8 years. The results revealed 21 nucleic acid alterations in the samples analyzed. The generated phylogenetic tree divided samples into two genotypes. Pre-core/Core mutations were significantly associated with the treatment received (P= 0.0.001) but not with laboratory parameters. Most samples were matched with the genotype D clade, while only four samples were positioned adjacent to the genotype E clade. Direct nucleic acid translation disclosed five nucleic acid variants (73T>G, 347T>G, 364A>G, 365T>C, and366A>G) on the core protein. Conclusions: This study has detected 21 nucleotide variants and 5 amino acid alterations within the coding sequences of the C gene. This study revealed that genotype D represents the primary genotype for the identified viral infections. The current study highlights the importance of these mutations evaluation for future, more comprehensive studies. [ABSTRACT FROM AUTHOR]

The new SARS-CoV-2 coronavirus, which emerged in late 2019, is a highly variable causative agent of COVID-19, a contagious respiratory disease with potentially severe complications. Vaccination is considered the most effective measure to prevent the spread and complications of this infection. Spike (S) protein-based vaccines were very successful in preventing COVID-19 caused by the ancestral SARS-CoV-2 strain; however, their efficacy was significantly reduced when coronavirus variants antigenically different from the original strain emerged in circulation. This is due to the high variability of this major viral antigen caused by escape from the immunity caused by the infection or vaccination with spike-targeting vaccines. The nucleocapsid protein (N) is a much more conserved SARS-CoV-2 antigen than the spike protein and has therefore attracted the attention of scientists as a promising target for broad-spectrum vaccine development. Here, we summarized the current data on various N-based COVID-19 vaccines that have been tested in animal challenge models or clinical trials. Despite the high conservatism of the N protein, escape mutations gradually occurring in the N sequence can affect its protective properties. During the three years of the pandemic, at least 12 mutations have arisen in the N sequence, affecting more than 40 known immunogenic T-cell epitopes, so the antigenicity of the N protein of recent SARS-CoV-2 variants may be altered. This fact should be taken into account as a limitation in the development of cross-reactive vaccines based on N-protein. [ABSTRACT FROM AUTHOR]

Annual vaccination is considered as the main preventive strategy against seasonal influenza. Due to the highly variable nature of major viral antigens, such as hemagglutinin (HA) and neuraminidase (NA), influenza vaccine strains should be regularly updated to antigenically match the circulating viruses. The influenza virus nucleoprotein (NP) is much more conserved than HA and NA, and thus seems to be a promising target for the design of improved influenza vaccines with broad cross-reactivity against antigenically diverse influenza viruses. Traditional subunit or recombinant protein influenza vaccines do not contain the NP antigen, whereas live-attenuated influenza vaccines (LAIVs) express the viral NP within infected cells, thus inducing strong NP-specific antibodies and T-cell responses. Many strategies have been explored to design broadly protective NP-based vaccines, mostly targeted at the T-cell mode of immunity. Although the NP is highly conserved, it still undergoes slow evolutionary changes due to selective immune pressure, meaning that the particular NP antigen selected for vaccine design may have a significant impact on the overall immunogenicity and efficacy of the vaccine candidate. In this review, we summarize existing data on the conservation of the influenza A viral nucleoprotein and review the results of preclinical and clinical trials of NP-targeting influenza vaccine prototypes, focusing on the ability of NP-specific immune responses to protect against diverse influenza viruses. [ABSTRACT FROM AUTHOR]

Introduction: Cytomegalovirus (CMV) is a common herpesvirus with a high prevalence worldwide. After the acute infection phase, CMV can remain latent in several tissues. CD8 T cells in the lungs and salivary glands mainly control its reactivation control. White adipose tissue (WAT) contains a significant population of memory T cells reactive to viral antigens, but CMV specificity has mainly been studied in mouse WAT. Therefore, we obtained blood, omental WAT (oWAT), subcutaneous WAT (sWAT), and liver samples from 11 obese donors to characterize the human WAT adaptive immune landscape from a phenotypic and immune receptor specificity perspective. Methods: We performed high-throughput sequencing of the T cell receptor (TCR) locus to analyze tissue and blood TCR repertoires of the 11 donors. The presence of TCRs specific to CMV epitopes was tested through ELISpot assays. Moreover, phenotypic characterization of T cells was carried out through flow cytometry. Results: High-throughput sequencing analyses revealed that tissue TCR repertoires in oWAT, sWAT, and liver samples were less diverse and dominated by hyperexpanded clones when compared to blood samples. Additionally, we predicted the presence of TCRs specific to viral epitopes, particularly from CMV, which was confirmed by ELISpot assays. Remarkably, we found that oWAT has a higher proportion of CMV-reactive T cells than blood or sWAT. Finally, flow cytometry analyses indicated that most WAT-infiltrated lymphocytes were tissue-resident effector memory CD8 T cells. Discussion: Overall, these findings postulate human oWAT as a major reservoir of CMV-specific T cells, presumably for latent viral reactivation control. This study enhances our understanding of the adaptive immune response in human WAT and highlights its potential role in antiviral defense. [ABSTRACT FROM AUTHOR]

Simple Summary: The H9N2 subtype is widespread worldwide and is endemic among low-pathogenic avian influenza (LPAIV) viruses in the Middle East, North Africa and Asia. The virulence of H9N2 viruses of Middle Eastern and North African origin was investigated by different methods (necropsy, histopathology, immunohistochemistry and quantitative RT-PCR). Clear difference was demonstrated between H9N2 isolates belonging to the same lineage (G1): A/chicken/Morocco/2021/2016 strain proved to be significantly more virulent than those of the Egyptian and Saudi Arabian ones, which showed no remarkable difference. Our study aimed to investigate the virulence of three recent H9N2 LPAIV strains belonging to the G1 lineage, isolated from field infections in North Africa and the Middle East. Three-week-old commercial broiler chickens (in total 62) were included and randomly allocated into three infected test groups and one control group. Each test group was inoculated intranasally/intratracheally with one of the three H9N2 isolates at a dose of 108 EID50 virus. The control group received phosphate-buffered saline (PBS) via the same route of application. The pathogenicity was evaluated based on clinical signs and gross pathological and histopathological lesions, the viral antigen load was assessed through immunohistochemistry staining (IHC), and a semi-quantitative detection of the genetic material was conducted via a real-time PCR. Our findings confirmed the obvious respiratory tract tropism of the virus strains with variable renal tropism. In contrast to the highly pathogenic AIVs, the tested H9N2 strains did not show replication in the central nervous system. The virus presence and lesions, mainly in the respiratory tract, were predominant on dpi 5 and significantly reduced or disappeared by dpi 11. A clear difference was demonstrated among the three isolates: the A/chicken/Morocco/2021/2016 strain proved to be significantly more virulent than the Egyptian and Saudi Arabian ones, which showed no remarkable difference. [ABSTRACT FROM AUTHOR]

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