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Introduction In light of the COVID-19 (Coronovirus Disease 2019) pandemic, the use of personal protective equipment has become essential to reduce viral transmission and maintain public health. Viruses, particularly human coronavirus and influenza, pose significant challenges because of their various transmission routes. UMF Corporation's innovation, Micrillon, aims to address these challenges by creating durable, antiviral technology for textiles without harmful chemicals, reducing viral transmission risks. Materials and Methods The study followed ISO Standard 18184:2019, testing Micrillon textiles against Human Coronavirus OC43 and H1N1 Influenza A virus using MDCK and HCT-8 cell lines. Cell propagation, viral application, TCID50 (Median Tissue Culture Infectious Dose) testing, and maintenance protocols were rigorously implemented to assess antiviral efficacy. Results Micrillon gloves, fabrics, and fibers exhibited high antiviral efficacy against both viruses across various contact times. Gloves demonstrated exceptional antiviral activity against H1N1 (99.88%) and OC43 (99.67%) at 120 minutes. Rolled fabrics showed strong efficacy against H1N1 (99.42% at 30 minutes) and OC43 (>97%) at all time points. Bundled fibers displayed substantial efficacy against H1N1 (99.17% at 120 minutes) and OC43 (>98%) at all time points. Conclusions The study demonstrates that Micrillon technology effectively inhibits viral activity, particularly in gloves, fabrics, and fibers. The innovation not only shows high antiviral efficacy against both Human Coronavirus and Influenza but also promises a reusable, sustainable solution, mitigating environmental impact and reducing the use of harmful chemicals in personal protective equipment. The technology holds promise for widespread use in health care and hospitality, offering a layer of protection while being environmentally conscious. Further development of such technologies can significantly reduce infection risks while minimizing environmental harm. [ABSTRACT FROM AUTHOR]

In this study, we evaluated the impact of human gut microbiota on the immune pathways in the respiratory tract using a gnotobiotic (Gn) piglet model. We humanized piglets with rural and urban infant fecal microbiota (RIFM and UIFM, respectively) and then infected them with a H1N1 swine influenza virus. We analyzed the microbial diversity and structure of the intestinal and respiratory tracts of the piglets before and after the influenza virus infection and measured the viral load and immune responses. We found that the viral load in the upper respiratory tract of UIFM transplanted piglets was higher than their rural cohorts (RIFM), while virus-specific antibody responses were comparable. The relative cytokine gene expression in the tracheobronchial (respiratory tract) and mesenteric (gastrointestinal) lymph nodes, lungs, blood, and spleen of RIFM and UIFM piglets revealed a trend in reciprocal regulation of proinflammatory, innate, and adaptive immune-associated cytokines as well as the frequency of T-helper/memory cells, cytotoxic T cells, and myeloid immune cell subsets. We also observed different phylum-level shifts of the fecal microbiota in response to influenza virus infection between the two piglet groups, suggesting the potential impact of the gut microbiota on the immune responses to influenza virus infection and lung microbiota. In conclusion, Gn piglets humanized with diverse infant fecal microbiota had differential immune regulation, with UIFM favoring the activation of proinflammatory immune mediators following an influenza virus infection compared to their rural RIFM cohorts. Furthermore, Gn piglets can be a useful model in investigating the impact of diverse human microbiota of the gastrointestinal tract, probably also the respiratory tract, on respiratory health and testing specific probiotic- or prebiotic-based therapeutics. [ABSTRACT FROM AUTHOR]

Background: Gamma-delta (γδ) T cells are a major immune cell subset in pigs. Approximately 50% of circulating T cells are γδ T cells in young pigs and up to 30% in adult sows. Despite this abundance, the functions of porcine γδ T cells are mostly unidentified. In humans and mice, activated γδ T cells exhibit broad innate cytotoxic activity against a wide variety of stressed, infected, and cancerous cells through death receptor/ligand-dependent and perforin/granzyme-dependent pathways. However, so far, it is unknown whether porcine γδ T cells have the ability to perform cytotoxic functions. Methods: In this study, we conducted a comprehensive phenotypic characterization of porcine γδ T cells isolated from blood, lung, and nasal mucosa. To further analyze the cytolytic potential of γδ T cells, in vitro cytotoxicity assays were performed using purified γδ T cells as effector cells and virus-exposed or mock-treated primary porcine alveolar macrophages as target cells. Results: Our results show that only CD2+ γδ T cells express cytotoxic markers (CD16, NKp46, perforin) with higher perforin and NKp46 expression in γδ T cells isolated from lung and nasal mucosa. Moreover, we found that γδ T cells can exhibit cytotoxic functions in a cell-cell contact and degranulation-dependent manner. However, porcine γδ T cells did not seem to specifically target Porcine Reproductive and Respiratory Syndrome Virus or swine Influenza A Virus-infected macrophages, which may be due to viral escape mechanisms. Conclusion: Porcine γδ T cells express cytotoxic markers and can exhibit cytotoxic activity in vitro. The specific mechanisms by which porcine γδ Tcells recognize target cells are not fully understood but may involve the detection of cellular stress signals. [ABSTRACT FROM AUTHOR]

A pyroelectric temperature sensor for measuring human body temperature with increased accuracy and speed for application in mobile robotic systems has been developed. This pyroelectric temperature sensor for measuring human body temperature is intended for use in various educational institutions. Its usage will allow for identifying sick or potentially ill people and providing them with preliminary advice and avoid infecting other people. This is particularly important considering the seasonality of dangerous infectious diseases and the emergence of new ones (e.g., COVID-19). It is also advisable to use this pyroelectric sensor in hospitals, where temperature measurement is very crucial for monitoring the course of various diseases. The proposed pyroelectric temperature sensor is based on a nonlinear oscillatory system, which provides high sensitivity and allows for solving the problem of increasing the accuracy of measuring the human body temperature in a non-contact way. Measurement error is ±0.1% in the operating range (32–43) °C, measurement time—1 s, and the frequency instability is 3·10−4. [ABSTRACT FROM AUTHOR]

This paper investigates the proposed 1493 zoonotic (swine influenza) pandemic that swept through the Spanish colony at La Isabela, Hispaniola. Primary and secondary accounts of the malady describe the attributed symptoms as summarized in the work of Guerra (1988) and attempt to predict the geographic spread of the zoonosis as a series of four expanding regional stages, beginning at La Isabela and nearby Indigenous villages, moving outward along known valley pathways, engulfing northern Hispaniola, and finally transporting the infectious disease to the nearby islands of Cuba, Puerto Rico, Jamaica, and the Bahama Archipelago, with the possibility of spreading to the Lesser Antilles, the eastern coast of Yucatan and Honduras, and the northern coast of South America. This proposed geographic virus dispersion model includes a series of island maps that locate selected archeological sites of known villages along with suggested travel times, providing a historical record of viral spread tracing. [ABSTRACT FROM AUTHOR]

Influenza D virus was isolated from pigs on a mixed pig and beef farm in France. Investigation suggested bullto-pig transmission and spread among pigs. The swine influenza D virus recovered was a reassortant of D/660 and D/OK lineages. Reported mutations in the receptor binding site might be related to swine host adaptation. [ABSTRACT FROM AUTHOR]

Influenza A virus (IAV) shows an extensive host range and rapid genomic variations, leading to continuous emergence of novel viruses with significant antigenic variations and the potential for cross-species transmission. This causes global pandemics and seasonal flu outbreaks, posing sustained threats worldwide. Thus, studying all IAVs' evolutionary patterns and underlying mechanisms is crucial for effective prevention and control. We developed FluTyping to identify IAV genotypes, to explore overall genetic diversity patterns and their restriction factors. FluTyping groups isolates based on genetic distance and phylogenetic relationships using whole genomes, enabling identification of each isolate's genotype. Three distinct genetic diversity patterns were observed: one genotype domination pattern comprising only H1N1 and H3N2 seasonal influenza subtypes, multi-genotypes co-circulation pattern including majority avian influenza subtypes and swine influenza H1N2, and hybrid-circulation pattern involving H7N9 and three H5 subtypes of influenza viruses. Furthermore, the IAVs in multi-genotypes co-circulation pattern showed region-specific dominant genotypes, implying the restriction of virus transmission is a key factor contributing to distinct genetic diversity patterns, and the genomic evolution underlying different patterns was more influenced by host-specific factors. In summary, a comprehensive picture of the evolutionary patterns of overall IAVs is provided by the FluTyping's identified genotypes, offering important theoretical foundations for future prevention and control of these viruses. [ABSTRACT FROM AUTHOR]

Swine influenza A virus (IAV-S) is a highly prevalent and transmissible pathogen infecting worldwide swine populations. Our previous work has shown that the computationally derived vaccine platform, Epigraph, can induce broadly cross-reactive and durable immunity against H3 IAV-S in mice and swine. Therefore, in this study, we assess the immunogenicity and protective efficacy of the Epigraph vaccine at increasingly lower doses to determine the minimum dose required to maintain protective immunity against three genetically divergent H3 IAV-S. We assessed both antibody and T cell responses and then challenged with three H3N2 IAV-S derived from either Cluster IV(A), Cluster I, or the 2010.1 "human-like" cluster and assessed protection through reduced pathology, reduced viral load in the lungs, and reduced viral shedding from nasal swabs. Overall, we observed a dose-dependent effect where the highest dose of Epigraph protected against all three challenges, the middle dose of Epigraph protected against more genetically similar IAV-S, and the lowest dose of Epigraph only protected against genetically similar IAV-S. The results of these studies can be used to continue developing a broadly protective and low-dose vaccine against H3 IAV-S. [ABSTRACT FROM AUTHOR]

Swine influenza A viruses (swIAV) cause an economically important respiratory disease in modern pig production. Continuous virus transmission and antigenic drift are difficult to control in enzootically infected pig herds. Here, antibody-positive piglets from a herd enzootically infected with swIAV H1N2 (clade 1 A.3.3.2) were immunized using a homologous prime-boost vaccination strategy with novel live attenuated influenza virus (LAIV) based on a reassortment-incompetent bat influenza-swIAV chimera or a vesicular stomatitis virus-based replicon vaccine. Challenge infection of vaccinated piglets by exposure to H1N2 swIAV-infected unvaccinated seeder pigs showed that both LAIV and replicon vaccine markedly reduced virus replication in the upper and lower respiratory tract, respectively, compared to piglets immunized with commercial heterologous or autologous adjuvanted whole-inactivated virus vaccines. Our novel vaccines may aid in interrupting continuous IAV transmission chains in large enzootically infected pig herds, improve the health status of the animals, and reduce the risk of zoonotic swIAV transmission. [ABSTRACT FROM AUTHOR]

Influenza viruses constitute a major threat to human health globally. The viral surface glycoprotein hemagglutinin (HA) is the immunodominant antigen, contains the site for binding to the cellular receptor (RBS), and it is the major target of neutralizing antibody responses post-infection. We developed llama-derived single chain antibody fragments (VHHs) specific for type A influenza virus. Four VHHs were identified and further characterized. VHH D81 bound residues in the proximity of the C-terminal region of HA1 of H1 and H5 subtypes, and showed weak neutralizing activity, whereas VHH B33 bound residues in the proximity of the N-terminal region of the HA's stem domain (HA2) of H1, H5, and H9 subtypes, and showed no neutralizing activity. Of most relevance, VHHs E13 and G41 recognized highly conserved conformational epitopes on the H1 HA's globular domain (HA1) and showed high virus neutralizing activity (ranging between 0.94 to 0.01μM), when tested against several human H1N1 isolates. Additionally, E13 displayed abrogated virus replication of a panel of H1N1 strains spanning over 80 years of antigenic drift and isolated from human, avian, and swine origin. Interestingly, E13 conferred protection in vivo at a dose as low as 0.05 mg/kg. Mice treated with E13 intranasally resulted in undetectable virus challenge loads in the lungs at day 4 post-challenge. The transfer of sterilizing pan-H1 immunity, by a dose in the range of micrograms given intranasally, is of major significance for a monomeric VHH and supports the further development of E13 as an immunotherapeutic agent for the mitigation of influenza infections. [ABSTRACT FROM AUTHOR]

Surprisingly, the 1977 "Russian flu" H1N1 pandemic influenza virus was genetically indistinguishable from strains that had circulated decades earlier but had gone extinct in 1957. This essay puts forward the most plausible chronology to explain the reemergence of the 1977 H1N1 pandemic virus: (1) in January–February 1976, a self-limited small outbreak of a swine H1N1 influenza virus occurred among Army personnel at Fort Dix, New Jersey; (2) in March 1976, the US launched a nationwide H1N1 swine influenza vaccine program; (3) other countries then also launched their own H1N1 R&D efforts; (4) a new H1N1 outbreak, genetically unrelated to the Fort Dix swine virus but indistinguishable from previously extinct H1N1 viruses, was detected early in 1977 in China; (5) the leading Chinese influenza virologist later disclosed that the Chinese military had conducted large H1N1 vaccine R&D studies in 1976. It is likely that the resurrected H1N1 influenza viruses were laboratory-stored strains that were unfrozen and studied as part of the emergency response to a perceived epidemic threat, and that accidentally escaped. The fear of a possible H1N1 pandemic was the critical factor that gave rise to the actual H1N1 pandemic, resulting in an avoidable "self-fulfilling prophecy pandemic." [ABSTRACT FROM AUTHOR]

Swine influenza viruses (SIVs) have been circulating in swine globally and are potential threats to human health. During the surveillance of SIVs in Shandong Province, China, from 2019 to 2022, 21 reassortant G4 genotype Eurasian avian-like (EA) H1N1 subtypes containing genes from the EA H1N1 (HA and NA), 2009 pandemic (pdm/09) H1N1 virus (PB2, PB1, PA, NP, and M), and classical swine (CS) H1N1 (NS) lineages were isolated. The analysis of the key functional amino acid sites in the isolated viruses showed that two mutation sites (190D and 225E) that preferentially bind to the human α2-6 sialic acid receptor were found in HA. In PB2, three mutation sites (271A, 590S, and 591R) that may increase mammalian fitness and a mutation site (431M) that increases pathogenicity in mice were found. A typical human signature marker that may promote infection in humans, 357K, was found in NP. The viruses could replicate efficiently in mouse lungs and turbinates, and one of the H1N1 isolates could replicate in mouse kidneys and brains without prior adaption, which indicates that the viruses potentially pose a threat to human health. Histopathological results showed that the isolated viruses caused typical bronchopneumonia and encephalitis in mice. The results indicate that G4 genotype H1N1 has potential transmissibility to humans, and surveillance should be enhanced, which could provide important information for assessing the pandemic potential of the viruses. [ABSTRACT FROM AUTHOR]

Influenza A virus outbreaks pose a significant burden to global health. However, detecting and subtyping the virus is challenging due to its high mutation rate, and it is difficult to distinguish viable viruses that cause infection from clinical samples. Here is a novel PMAxx-LAMP assay for the classification of viable and non-viable Influenza A virus together with differentiation between H1N1 and H3N2 subtypes. Our loop-mediated isothermal amplification (LAMP) primers displayed limits of detection of 102 copies/μL for both subtypes, high specificity, reproducibility, and good linearity with correlation coefficients of 0.9762 and 0.9901 for H1N1 and H3N2, respectively. PMAxx effectively distinguished between viable and non-viable viruses at an optimal concentration of 10 μM. In the LAMP method, the clinical specificity and sensitivity for the H1N1 subtype were both 100%, while for the H3N2 subtype, they were 94.44 and 92.31%, respectively. With the PMAxx-LAMP assay, the clinical specificity and sensitivity were 68% and 65% for the H1N1 subtype, and 81% and 69% for the H3N2 subtype, respectively. The reduced clinical specificity and sensitivity observed in the PMAxx-LAMP assay can be attributed to the presence of non-viable viruses, which are labeled with PMAxx and subsequently eliminated from positive samples. The PMAxx-LAMP offers potential benefits in determining the stage of infection, enabling early screening of patients, and shortening the window period for virus detection. The simplicity and efficiency of this assay make it suitable for use in resource limited settings and point-of-care (POCT) applications. [ABSTRACT FROM AUTHOR]

This study described the results of a surveillance program monitoring circulation of influenza A viruses among domestic pigs (Sus domesticus) in Kazakhstan during 2018--2021. PCR data derived from 2,513 samples (nasopharyngeal swabs) collected from swine on large pig complexes and peasant farms located in different regions of Kazakhstan revealed that about 5% of samples were positive for influenza A virus RNA. This result suggested low levels of influenza A virus circulation in Kazakhstan. Subtyping of a set of samples revealed that the main strains circulating in 2018--2019 were A/H1N1 and A/H3N2. Surveillance conducted in 2020--2021 identified only A/H1N1 viruses in swine. The PCR data were confirmed by isolation of six strains: five influenza A/H1N1 viruses and one A/H3N2 virus. [ABSTRACT FROM AUTHOR]

Background: Infection by porcine respiratory and reproductive syncytial virus (PRRSV), swine influenza virus (SIV) and porcine epidemic diarrhea (PEDV) adversely affect worldwide pig production. Because effective control remains elusive the present research was designed to explore the in vitro antiviral activity of oleandrin and an N. oleander extract (PBI-05204) against each porcine virus. Methods: Monkey kidney (MARK-145) cells, Madin-Darby canine kidney cells (MDCK), and African green monkey kidney cells (VERO 76) were used for in vitro culture systems for PRRSV, SIV and PEDV, respectively. Cytotoxicity was established using serial dilutions of oleandrin or PBI-05204. Noncytotoxic concentrations of each product were used either prior to or at 12 h and 24 h following exposure to corresponding viruses. Infectious virus titers were also determined. Results: Oleandrin and PBI-05204 demonstrated strong antiviral activity against PRRSV, SIV and PEDV when added prior to or following infection of cells. Determination of viral loads by PCR demonstrated a decline in PRRSV replication reaching 99.57% and 99.79% for oleandrin and PBI-05204, respectively, and decrease of 95.36% and 99.54% in infectivity of progeny virus in PRRSV infected cultures. Similarly, oleandrin tested against SIV and PEDV was effective in near complete inhibition of infectious virus production. Conclusion: The research demonstrates the potency of oleandrin and PBI-05204 to inhibit infectivity of three important porcine viruses. These data showing non-toxic concentrations of oleandrin as a single common agent for inhibiting infectivity of the three different porcine viruses tested here support further investigation of antiviral efficacy and possible in vivo use. [ABSTRACT FROM AUTHOR]

Influenza A viruses in swine have considerable genetic diversity and continue to pose a pandemic threat to humans due to a potential lack of population level immunity. Here we describe a pipeline to characterize and triage influenza viruses for their pandemic risk and examine the pandemic potential of two widespread swine origin viruses. Our analysis reveals that a panel of human sera collected from healthy adults in 2020 has no cross-reactive neutralizing antibodies against a α-H1 clade strain (α-swH1N2) but do against a γ-H1 clade strain. The α-swH1N2 virus replicates efficiently in human airway cultures and exhibits phenotypic signatures similar to the human H1N1 pandemic strain from 2009 (H1N1pdm09). Furthermore, α-swH1N2 is capable of efficient airborne transmission to both naïve ferrets and ferrets with prior seasonal influenza immunity. Ferrets with H1N1pdm09 pre-existing immunity show reduced α-swH1N2 viral shedding and less severe disease signs. Despite this, H1N1pdm09-immune ferrets that became infected via the air can still onward transmit α-swH1N2 with an efficiency of 50%. These results indicate that this α-swH1N2 strain has a higher pandemic potential, but a moderate level of impact since there is reduced replication fitness and pathology in animals with prior immunity. Influenza A viruses pose a continuing pandemic threat to humans. Le Sage, et al. describe a pandemic triage pipeline to evaluate the pandemic risk of emerging viruses and utilize it to characterize two widespread swine influenza A viruses. [ABSTRACT FROM AUTHOR]

Pig farming has become a strategically significant and economically important industry across the globe. It is also a potentially vulnerable sector due to challenges posed by transboundary diseases in which viral infections are at the forefront. Among the porcine viral diseases, African swine fever, classical swine fever, foot and mouth disease, porcine reproductive and respiratory syndrome, pseudorabies, swine influenza, and transmissible gastroenteritis are some of the diseases that cause substantial economic losses in the pig industry. It is a well-established fact that vaccination is undoubtedly the most effective strategy to control viral infections in animals. From the period of Jenner and Pasteur to the recent new-generation technology era, the development of vaccines has contributed significantly to reducing the burden of viral infections on animals and humans. Inactivated and modified live viral vaccines provide partial protection against key pathogens. However, there is a need to improve these vaccines to address emerging infections more comprehensively and ensure their safety. The recent reports on new-generation vaccines against swine viruses like DNA, viral-vector-based replicon, chimeric, peptide, plant-made, virus-like particle, and nanoparticle-based vaccines are very encouraging. The current review gathers comprehensive information on the available vaccines and the future perspectives on porcine viral vaccines. [ABSTRACT FROM AUTHOR]

Background: H1N1 is one of the major subtypes of influenza A virus (IAV) that causes seasonal influenza, posing a serious threat to human health. A traditional Chinese medicine combination called Qingxing granules (QX) is utilized clinically to treat epidemic influenza. However, its chemical components are complex, and the potential pharmacological mechanisms are still unknown. Methods: QX's effective components were gathered from the TCMSP database based on two criteria: drug-likeness (DL ≥ 0.18) and oral bioavailability (OB ≥ 30%). SwissADME was used to predict potential targets of effective components, and Cytoscape was used to create a "Herb-Component-Target" network for QX. In addition, targets associated with H1N1 were gathered from the databases GeneCards, OMIM, and GEO. Targets associated with autophagy were retrieved from the KEGG, HAMdb, and HADb databases. Intersection targets for QX, H1N1 influenza, and autophagy were identified using Venn diagrams. Afterward, key targets were screened using Cytoscape's protein–protein interaction networks built using the database STRING. Biological functions and signaling pathways of overlapping targets were observed through GO analysis and KEGG enrichment analysis. The main chemical components of QX were determined by high-performance liquid chromatography (HPLC), followed by molecular docking. Finally, the mechanism of QX in treating H1N1 was validated through animal experiments. Results: A total of 786 potential targets and 91 effective components of QX were identified. There were 5420 targets related to H1N1 and 821 autophagy-related targets. The intersection of all targets of QX, H1N1, and autophagy yielded 75 intersecting targets. Ultimately, 10 core targets were selected: BCL2, CASP3, NFKB1, MTOR, JUN, TNF, HSP90AA1, EGFR, HIF1A, and MAPK3. Identification of the main chemical components of QX by HPLC resulted in the separation of seven marker ingredients within 195 min, which are amygdalin, puerarin, baicalin, phillyrin, wogonoside, baicalein, and wogonin. Molecular docking results showed that BCL2, CASP3, NFKB1, and MTOR could bind well with the compounds. In animal studies, QX reduced the degenerative alterations in the lung tissue of H1N1-infected mice by upregulating the expression of p-mTOR/mTOR and p62 and downregulating the expression of LC3, which inhibited autophagy. Conclusions: According to this study's network pharmacology analysis and experimental confirmation, QX may be able to treat H1N1 infection by regulating autophagy, lowering the expression of LC3, and increasing the expression of p62 and p-mTOR/mTOR. [ABSTRACT FROM AUTHOR]

Introduction: Swine influenza viruses (SIVs) pose significant economic losses to the pig industry and are a burden on global public health systems. The increasing complexity of the distribution and evolution of different serotypes of influenza strains in swine herds escalates the potential for the emergence of novel pandemic viruses, so it is essential to develop new vaccines based on swine influenza. Methods: Here, we constructed a self-assembling ferritin nanoparticle vaccine based on the hemagglutinin (HA) extracellular domain of swine influenza A (H1N1) virus using insect baculovirus expression vector system (IBEVS), and after two immunizations, the immunogenicities and protective efficacies of the HA-Ferritin nanoparticle vaccine against the swine influenza virus H1N1 strain in mice and piglets were evaluated. Results: Our results demonstrated that HA-Ferritin nanoparticle vaccine induced more efficient immunity than traditional swine influenza vaccines. Vaccination with the HA-Ferritin nanoparticle vaccine elicited robust hemagglutinin inhibition titers and antigen-specific IgG antibodies and increased cytokine levels in serum. MF59 adjuvant can significantly promote the humoral immunity of HA-Ferritin nanoparticle vaccine. Furthermore, challenge tests showed that HA-Ferritin nanoparticle vaccine conferred full protection against lethal challenge with H1N1 virus and significantly decreased the severity of virus-associated lung lesions after challenge in both BALB/c mice and piglets. Conclusion: Taken together, these results indicate that the hemagglutinin extracellular-based ferritin nanoparticle vaccine may be a promising vaccine candidate against SIVs infection. [ABSTRACT FROM AUTHOR]

This study focuses on the development and characterization of an intranasal vaccine platform using adjuvanted nanoparticulate delivery of swine influenza A virus (SwIAV). The vaccine employed whole inactivated H1N2 SwIAV as an antigen and STING-agonist ADU-S100 as an adjuvant, with both surface adsorbed or encapsulated in mannose–chitosan nanoparticles (mChit-NPs). Optimization of mChit-NPs included evaluating size, zeta potential, and cytotoxicity, with a 1:9 mass ratio of antigen to NP demonstrating high loading efficacy and non-cytotoxic properties suitable for intranasal vaccination. In a heterologous H1N1 pig challenge trial, the mChit-NP intranasal vaccine induced cross-reactive sIgA antibodies in the respiratory tract, surpassing those of a commercial SwIAV vaccine. The encapsulated mChit-NP vaccine induced high virus-specific neutralizing antibody and robust cellular immune responses, while the adsorbed vaccine elicited specific high IgG and hemagglutinin inhibition antibodies. Importantly, both the mChit-NP vaccines reduced challenge heterologous viral replication in the nasal cavity higher than commercial swine influenza vaccine. In summary, a novel intranasal mChit-NP vaccine platform activated both the arms of the immune system and is a significant advancement in swine influenza vaccine design, demonstrating its potential effectiveness for pig immunization. [ABSTRACT FROM AUTHOR]

Background: This study investigated cause-specific mortality rates in 12 countries during the COVID-19 pandemic in 2020 and 2021. Methods: We collected weekly cause-specific mortality data from respiratory disease, pneumonia, cardiovascular disease (CVD) and cancer from national vital statistic databases. We calculated excess mortality for respiratory disease (excluding COVID-19 codes), pneumonia, and CVD in 2020 and 2021 by comparing observed weekly against expected mortality based on historical data (2015–2019), accounting for seasonal trends. We used multilevel regression models to investigate the association between country-level pandemic-related variables and cause-specific mortality. Results: Significant reductions in cumulative mortality from respiratory disease and pneumonia were observed in 2020 and/or 2021, except for Georgia, Northern Ireland, Kazakhstan, and Ukraine, which exhibited excess mortality for one or both causes. Australia, Austria, Cyprus, Georgia, and Northern Ireland experienced excess cumulative CVD mortality in 2020 and/or 2021. Australia, Austria, Brazil, Cyprus, Georgia, Northern Ireland, Scotland and Slovenia, experienced increased crude cumulative cancer mortality during 2020 and/or 2021 compared to previous years. Among pandemic-related variables, reported COVID-19 incidence was negatively associated with increased cancer mortality, excess respiratory, (2020) and pneumonia (2021) mortality, and positively associated with respiratory and CVD mortality (2021). Stringency of control measures were negatively associated with excess respiratory disease, CVD, and increased cancer mortality (2021). Conclusions: This study provides evidence of substantial excess mortality from CVD, and notable reductions in respiratory disease and pneumonia in both years across most countries investigated. Our study also highlights the beneficial impact of stringent control measures in mitigating excess mortality from most causes in 2021. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic led to 231,841 deaths and 940,243 hospitalisations in England, by the end of March 2023. This paper calculates the real-time infection hospitalisation risk (IHR) and infection fatality risk (IFR) using the Office for National Statistics Coronavirus Infection Survey (ONS CIS) and the Real-time Assessment of Community Transmission Survey between November 2020 to March 2023. The IHR and the IFR in England peaked in January 2021 at 3.39% (95% Credible Intervals (CrI): 2.79, 3.97) and 0.97% (95% CrI: 0.62, 1.36), respectively. After this time, there was a rapid decline in the severity from infection, with the lowest estimated IHR of 0.32% (95% CrI: 0.27, 0.39) in December 2022 and IFR of 0.06% (95% CrI: 0.04, 0.08) in April 2022. We found infection severity to vary more markedly between regions early in the pandemic however, the absolute heterogeneity has since reduced. The risk from infection of SARS-CoV-2 has changed substantially throughout the COVID-19 pandemic with a decline of 86.03% (80.86, 89.35) and 89.67% (80.18, 93.93) in the IHR and IFR, respectively, since early 2021. From April 2022 until March 2023, the end of the ONS CIS study, we found fluctuating patterns in the severity of infection with the resumption of more normative mixing, resurgent epidemic waves, patterns of waning immunity, and emerging variants that have shown signs of convergent evolution. The severity of SARS-CoV-2 infection varied over the course of the pandemic due to factors such as changes in variant characteristics and population immunity from previous infection or vaccination. Here, the authors estimate infection hospitalisation and infection fatality rates in England over time from the start of the pandemic until March 2023. [ABSTRACT FROM AUTHOR]

In 2020, a new genotype of swine H1N2 influenza virus (H1avN2–HA 1C.2.4) was identified in France. It rapidly spread within the pig population and supplanted the previously predominant H1avN1-HA 1C.2.1 virus. To characterize this new genotype which is genetically and antigenically distant from the other H1avNx viruses detected in France, an experimental study was conducted to compare the outcomes of H1avN2 and H1avN1 infections in pigs and evaluate the protection conferred by the only inactivated vaccine currently licensed in Europe containing an HA 1C (clade 1C.2.2) antigen. Infection with H1avN2 induced stronger clinical signs and earlier shedding than H1avN1. The neutralizing antibodies produced following H1avN2 infection were unable to neutralize H1avN1, and vice versa, whereas the cellular-mediated immunity cross-reacted. Vaccination slightly altered the impact of H1avN2 infection at the clinical level, but did not prevent shedding of infectious virus particles. It induced a cellular-mediated immune response towards H1avN2, but did not produce neutralizing antibodies against this virus. As in vaccinated animals, animals previously infected by H1avN1 developed a cross-reacting cellular immune response but no neutralizing antibodies against H1avN2. However, H1avN1 pre-infection induced a better protection against the H1avN2 infection than vaccination, probably due to higher levels of non-neutralizing antibodies and a mucosal immunity. Altogether, these results showed that the new H1avN2 genotype induced a severe respiratory infection and that the actual vaccine was less effective against this H1avN2-HA 1C.2.4 than against H1avN1-HA 1C.2.1, which may have contributed to the H1avN2 epizootic and dissemination in pig farms in France. [ABSTRACT FROM AUTHOR]

Background: Monitoring of infectious diseases on swine farms requires a high diagnostic sensitivity and specificity of the test system. Moreover, particularly in cases of swine influenza A virus (swIAV) it is desirable to include characterization of the virus as precisely as possible. This is indispensable for strategies concerning prophylaxis of swIAV and furthermore, to meet the requirements of a purposeful monitoring of newly emerging swIAV strains in terms of vaccine design and public health. Within the present cross-sectional study, we compared the diagnostic value of group samples (wipes of surfaces with direct contact to mouth/nose, dust wipes, udder skin wipes, oral fluids) to individual samples (nasal swabs, tracheobronchial swabs) for both swIAV identification and characterization. Sampling included different stages of pig production on 25 sow farms with attached nursery considered as enzootically infected with swIAV. Firstly, samples were analyzed for IAV genome and subsequently samples with Ct-values < 32 were subtyped by multiplex RT-qPCR. Results: Nasal swabs of suckling piglets and nursery pigs resulted in a higher odds to detect swIAV (p < 0.001) and to identify swIAV subtypes by RT-qPCR (p < 0.05) compared to nasal swabs of sows. In suckling piglets, significant higher rates of swIAV detection could be observed for nasal swabs (p = 0.007) and sow udder skin wipes (p = 0.036) compared to contact wipes. In the nursery, group sampling specimens were significantly more often swIAV positive compared to individual samples (p < 0.01), with exception of the comparison between contact wipes and nasal swabs (p = 0.181). However, in general nasal swabs were more likely to have Ct-value < 32 and thus, to be suitable for subtyping by RT-qPCR compared to dust wipes, contact wipes, udder skin wipes and tracheobronchial swabs (p < 0.05). Interestingly, different subtypes were found in different age groups as well as in different specimens in the same holding. Conclusion: Although population-based specimens are highly effective for swIAV monitoring, nasal swabs are still the preferable sampling material for the surveillance of on-farm circulating strains due to significantly higher virus loads. Remarkably, sampling strategies should incorporate suckling piglets and different age groups within the nursery to cover as many as possible of the on-farm circulating strains. [ABSTRACT FROM AUTHOR]

Background: The transmission of influenza virus in households, especially by children, is a major route of infection. Prior studies suggest that timely antiviral treatment of ill cases may reduce infection in household contacts. The aim of the study was to compare the effects of oseltamivir (OTV) and baloxavir marboxil (BXM) treatment of index cases on the secondary attack rate (SAR) of influenza within household. Methods: A post hoc analysis was done in BLOCKSTONE trial—a placebo‐controlled, double‐blinded post‐exposure prophylaxis of BXM. Data were derived from the laboratory‐confirmed index cases' household contacts who received placebo in the trial and also from household members who did not participate in the trial but completed illness questionnaires. To assess the SAR of household members, multivariate analyses adjusted for factors including age, vaccination status, and household size were performed and compared between contacts of index cases treated with BXM or OTV. Results: In total, 185 index cases (116 treated with BXM and 69 treated with OTV) and 410 household contacts (201 from trial, 209 by questionnaire) were included. The Poisson regression modeling showed that the SAR in household contacts of index cases treated with BXM and OTV was 10.8% and 18.5%, respectively; the adjusted relative reduction in SAR was 41.8% (95% confidence interval: 1.0%–65.7%, p = 0.0456) greater with BXM than OTV. Similar reductions were found in contacts from the trial and those included by questionnaire. Conclusion: BXM treatment of index cases appeared to result in a greater reduction in secondary household transmission than OTV treatment. [ABSTRACT FROM AUTHOR]

Novel swine Influenza A viruses (IAVs) have been described in South America. The objective of this study was to evaluate the replication kinetics of novel swine IAVs as a first step in vaccine production. Different swine IAV lineages (H1N1, H1N2, and H3N2), infection doses (MOI: 1, 0.1, 0.01, 0.001, 0.0001, and 0.00001), harvest times (every 12 h), and substrates (MDCK and Vero cells) were used. For all IAV strains, MDCK cells were the most efficient substrate, generating titers of =128 HAU/50 µL with an MOI of 0.00001 at 60 h post-infection. These data may be useful in vaccineproducing laboratories. [ABSTRACT FROM AUTHOR]

Although the World Health Organization has declared that the COVID‐19 pandemic no longer qualifies as a global public health emergency, it still needs to explore the response of society to the COVID‐19 pandemic. Socio‐economic status (SES) was proven to be linearly associated with the COVID‐19 pandemic, although this relationship may be more complex due to regional differences. In the study, we analyzed and revealed the effects and mechanisms of SES on infections among low, lower‐middle, upper‐middle and high SES group (LSG, LMSG, UMSG, and HSG, respectively). The results showed that the relationship between SES and infections was inverted U‐shaped, especially in the first three phases. In Phase I, UMSG had the highest number of infections, with an average of 238.31/1M people (95%CI: 135.47–341.15/1M people). In Phases II and III, infections decreased insignificantly with increasing SES (r = −0.01, p = 0.92; r = −0.11, p = 0.22) and the highest number of infections were found in the LMSG. In Phase IV, SES was positively related to the number of infections (r = 0.54, p < 0.001). Furthermore, the nonlinear impact of multiple factors related to SES on the infections explains the complex relationships between SES and infections. SES affected infections mainly through medical resources, demographics and vaccination, and differed across the SES groups. Particularly, demographics could exert an impact on population mobility, subsequently influencing infections in LMSG, with an indirect effect of 0.01 (p < 0.05) in Phase II. This study argues for greater attention to countries with middle SES and the need for future targeted measures to cope with infectious diseases. Plain Language Summary: As the virulence of SARS‐CoV‐2 diminishes and vaccination coverage rises, countries around the world are gradually returning to normal development like the pre‐COVID‐19 period. However, the COVID‐19 pandemic crisis of the past three years calls for thoughtful reflection, presenting us with experiences and lessons to learn from. Previous studies suggested that the infections were linearly associated with socio‐economic status (SES). Nevertheless, SES was related with multiple factors (such as vaccination), leading to the complex relationship between infections and SES. Therefore, it still needs to analyze the impacts and mechanisms of SES on infections. Empirical results show the relationship between SES and infections was an inverted U‐shape in the progress of the COVID‐19 pandemic, and the infections in lower‐middle and upper‐middle SES countries was the highest in the first three phases. SES affected infections through multiple factors and the mechanisms differed across SES groups. This work emphasizes the need to be attentive to the further prevalence of infectious diseases in middle‐SES countries and implementing the target measures in different SES countries in the future. Key Points: The response of society to the COVID‐19 pandemic was exploredSocio‐economic status had an inverted U‐shaped relationship with infections during the COVID‐19 pandemicSES affected infections mainly through action time, demographics, medical resources and vaccination [ABSTRACT FROM AUTHOR]

Research about science and publics in the COVID-19 pandemic often focuses on public trust and on identifying and correcting public attitudes. Drawing on qualitative interviews with 209 residents in six countries—Austria, Bolivia, Germany, Italy, Mexico, and Portugal—this article uses the concept of performativity to explore how participants understand, and relate to science, in the COVID-19 context. By performativity, we mean the ways by which participants understand themselves as particular sorts of publics through identification with, and differentiation from, various other actors in matters that are perceived as controversies surrounding science: COVID-19 vaccination, media communication of science, and the interactions between governments and scientists. The criteria used to construct the similarities and differences among publics were heterogeneous and fluid, showing how epistemic beliefs about the nature of, and trust in, scientific knowledge are intermingled with social and cultural memberships embedded in specific contexts and across disparate places. [ABSTRACT FROM AUTHOR]

Swine Influenza A Virus (IAV-S) imposes a significant impact on the pork industry and has been deemed a significant threat to global public health due to its zoonotic potential. The most effective method of preventing IAV-S is vaccination. While there are tremendous efforts to control and prevent IAV-S in vulnerable swine populations, there are considerable challenges in developing a broadly protective vaccine against IAV-S. These challenges include the consistent diversification of IAV-S, increasing the strength and breadth of adaptive immune responses elicited by vaccination, interfering maternal antibody responses, and the induction of vaccine-associated enhanced respiratory disease after vaccination. Current vaccination strategies are often not updated frequently enough to address the continuously evolving nature of IAV-S, fail to induce broadly cross-reactive responses, are susceptible to interference, may enhance respiratory disease, and can be expensive to produce. Here, we review the challenges and current status of universal IAV-S vaccine research. We also detail the current standard of licensed vaccines and their limitations in the field. Finally, we review recently described novel vaccines and vaccine platforms that may improve upon current methods of IAV-S control. [ABSTRACT FROM AUTHOR]

Introduction: Systematic evaluation of long-term outcomes in survivors of H1N1 is still lacking. This study aimed to characterize long-term outcomes of severe H1N1-induced pneumonia and acute respiratory distress syndrome (ARDS). Method: This was a single-center, prospective, cohort study. Survivors were followed up for four times after discharge from intensive care unit (ICU) by lung high-resolution computed tomography (HRCT), pulmonary function assessment, 6-minute walk test (6MWT), and SF-36 instrument. Result: A total of 60 survivors of H1N1-induced pneumonia and ARDS were followed up for four times. The carbon monoxide at single breath (DLCO) of predicted values and the 6MWT results didn't continue improving after 3 months. Health-related quality of life didn't change during the 12 months after ICU discharge. Reticulation or interlobular septal thickening on HRCT did not begin to improve significantly until the 12-month follow-up. The DLCO of predicted values showed negative correlation with the severity degree of primary disease and reticulation or interlobular septal thickening, and a positive correlation with physical functioning. The DLCO of predicted values and reticulation or interlobular septal thickening both correlated with the highest tidal volume during mechanical ventilation. Levels of fibrogenic cytokines had a positive correlation with reticulation or interlobular septal thickening. Conclusion: The improvements in pulmonary function and exercise capacity, imaging, and health-related quality of life had different time phase and impact on each other during 12 months of follow-up. Long-term outcomes of pulmonary fibrosis might be related to the lung injury and excessive lung fibroproliferation at the early stage during ICU admission. [ABSTRACT FROM AUTHOR]

Background: With increased attention to the importance of integrating the One Health approach into zoonotic disease surveillance and response, a greater understanding of the mechanisms to support effective communication and information sharing across animal and human health sectors is needed. The objectives of this qualitative case study were to describe the communication channels used between human and animal health stakeholders and to identify the elements that have enabled the integration of the One Health approach. Methods: We combined documentary research with interviews with fifteen stakeholders to map the communication channels used in human and swine influenza surveillance in Alberta, Canada, as well as in the response to a human case of H1N2v in 2020. A thematic analysis of the interviews was also used to identify the barriers and facilitators to communication among stakeholders from the animal and human health sectors. Results: When a human case of swine influenza emerged, the response led by the provincial Chief Medical Officer of Health involved players at various levels of government and in the human and animal health sectors. The collaboration of public and animal health laboratories and of the swine sector, in addition to the information available through the surveillance systems in place, was swift and effective. Elements identified as enabling smooth communication between the human and animal health systems included preexisting relationships between the various stakeholders, a relationship of trust between them (e.g., the swine sector and their perception of government structures), the presence of stakeholders acting as permanent liaisons between the ministries of health and agriculture, and stakeholders' understanding of the importance of the One Health approach. Conclusions: Information flows through formal and informal channels and both structural and relational features that can support rapid and effective communication in infectious disease surveillance and outbreak response. [ABSTRACT FROM AUTHOR]

• Optimizing and scaling up the monoglycosylated vaccine production process for clinical trials and future product development. • IVR-190 mg presents comparable stability with fully glycosylated IVR-190 virus vaccine. • IVR-190 mg induced substantial cross-strain HA- and NA-inhibiting antibody responses. • Toxicology study provides safety profiles for IVR-190 mg for further clinical study. The yearly epidemics and unpredictable outbreaks of influenza have raised serious concerns globally and led to prioritizing the development of an effective vaccine to protect against newly emerging variants. Previously, we demonstrated that monoglycosylated influenza virus vaccines derived from A/California/7/2009 or an updated A/Brisbane/02/2018 (IVR-190) vaccine strain recommended by WHO are superior to fully glycosylated vaccines and could broadly protect against past and new coming H1N1 variants. However, whether such a monoglycosylated virus vaccine can be mass-produced to meet clinical demands and stable enough to provide consistent efficacy against H1N1 viruses remains unclear. Herein, we developed a platform for the pilot-scale production of the monoglycosylated split virus vaccine from the IVR-190 strain (IVR-190 mg) with a robust and cost-effective manufacturing process. The critical parameters of inoculum dose, concentration of kifunensine, and optimized Endo H treatment process were comprehensively investigated. Several aims for preclinical studies of IVR-190 mg were achieved, including [i] the execution of three engineering batch runs to validate lot-to-lot consistency, [ii] the establishment of IVR-190 mg specifications to meet the acceptance criteria of a conventional influenza vaccine, [iii] an investigation of the stability profile of IVR-190 mg , and completion of a safety evaluation by conducting an animal toxicology study. The toxicology study under GLP guidance found no systemic toxicity after rabbits were vaccinated with IVR-190 mg. The serological data showed that IVR-190 mg is highly immunogenic and effective in inducing a cross-strain protective level of antibody immune responses, including hemagglutination-inhibition titers, viral neutralization activity, and broad HA- and NA-inhibiting antibody titers against past and new H1N1 viruses. In conclusion, this study provides efficacy and safety profiles of IVR-190 mg for further clinical study and shows that this vaccine without a glycan shield has great potential to be safe and protective against H1N1 variants. [ABSTRACT FROM AUTHOR]

Background: Accurate estimates of the COVID-19 pandemic's indirect impacts are crucial, especially in low- and middle-income countries. This study aims to update estimates of excess maternal deaths in Brazil during the first two years of the COVID-19 pandemic. Methods: This was an exploratory mixed ecological study using the counterfactual approach. The observed maternal deaths were gathered from the Mortality Information System (SIM) for the period between March 2015 and February 2022. Expected deaths from March 2020 to February 2022 were estimated using quasipoisson generalized additive models, considering quadrimester, age group, and their interaction as predictor variables. Analyses were performed in R version 4.1.2, RStudio, version 2023.03.1+446 and carried out with support from the "mgcv" and "plot_model" libraries. Results: A total of 5,040 maternal deaths were reported, with varying excess mortality across regions and age groups, resulting in 69% excess maternal mortality throughout Brazil during the first two years of the pandemic. The Southeast region had 50% excess mortality throughout the first two years and 76% excess in the second year. The North region had 69% excess mortality, increasing in the second year, particularly among women aged 20–34. The Northeast region showed 80% excess mortality, with a significant increase in the second year, especially among women aged 35–49. The Central-West region had 75% excess mortality, higher in the second year and statistically significant among women aged 35–49. The South region showed 117% excess mortality, reaching 203% in the second year among women aged 20–34, but no excess mortality in the 10–19 age category. Conclusions: Over two years, Brazil saw a significant impact on maternal excess deaths, regardless of region and pandemic year. The highest peak occurred between March and June 2021, emphasizing the importance of timely and effective epidemic responses to prevent avoidable deaths and prepare for new crises. [ABSTRACT FROM AUTHOR]

Swine influenza A viruses pose a public health concern as novel and circulating strains occasionally spill over into human hosts, with the potential to cause disease. Crucial to preempting these events is the use of a threat assessment framework for human populations. However, established guidelines do not specify which animal models or in vitro substrates should be used. We completed an assessment of a contemporary swine influenza isolate, A/swine/GA/A27480/2019 (H1N2), using animal models and human cell substrates. Infection studies in vivo revealed high replicative ability and a pathogenic phenotype in the swine host, with replication corresponding to a complementary study performed in swine primary respiratory epithelial cells. However, replication was limited in human primary cell substrates. This contrasted with our findings in the Calu-3 cell line, which demonstrated a replication profile on par with the 2009 pandemic H1N1 virus. These data suggest that the selection of models is important for meaningful risk assessment. [ABSTRACT FROM AUTHOR]

Rapid and early detection of infectious diseases in pigs is important, especially for the implementation of control measures in suspected cases of African swine fever (ASF), as an effective and safe vaccine is not yet available in most of the affected countries. Additionally, analysis for swine influenza is of significance due to its high morbidity rate (up to 100%) despite a lower mortality rate compared to ASF. The wide distribution of swine influenza A virus (SwIAV) across various countries, the emergence of constantly new recombinant strains, and the danger of human infection underscore the need for rapid and accurate diagnosis. Several diagnostic approaches and commercial methods should be applied depending on the scenario, type of sample and the objective of the studies being implemented. At the early diagnosis of an outbreak, virus genome detection using a variety of PCR assays proves to be the most sensitive and specific technique. As the disease evolves, serology gains diagnostic value, as specific antibodies appear later in the course of the disease (after 7–10 days post-infection (DPI) for ASF and between 10–21 DPI for SwIAV). The ongoing development of commercial kits with enhanced sensitivity and specificity is evident. This review aims to analyse recent advances and current commercial kits utilised for the diagnosis of ASF and SwIAV. [ABSTRACT FROM AUTHOR]

Genetically modified pigs play a critical role in mimicking human diseases, xenotransplantation, and the development of pigs resistant to viral diseases. The use of programmable endonucleases, including the CRISPR/Cas9 system, has revolutionized the generation of genetically modified pigs. This study evaluates the efficiency of electroporation of oocytes prior to fertilization in generating edited gene embryos for different models. For single gene editing, phospholipase C zeta (PLC ζ) and fused in sarcoma (FUS) genes were used, and the concentration of sgRNA and Cas9 complexes was optimized. The results showed that increasing the concentration resulted in higher mutation rates without affecting the blastocyst rate. Electroporation produced double knockouts for the TPC1/TPC2 genes with high efficiency (79 %). In addition, resistance to viral diseases such as PRRS and swine influenza was achieved by electroporation, allowing the generation of double knockout embryo pigs (63 %). The study also demonstrated the potential for multiple gene editing in a single step using electroporation, which is relevant for xenotransplantation. The technique resulted in the simultaneous mutation of 5 genes (GGTA1, B4GALNT2, pseudo B4GALNT2, CMAH and GHR). Overall, electroporation proved to be an efficient and versatile method to generate genetically modified embryonic pigs, offering significant advances in biomedical and agricultural research, xenotransplantation, and disease resistance. Electroporation led to the processing of numerous oocytes in a single session using less expensive equipment. We confirmed the generation of gene-edited porcine embryos for single, double, or quintuple genes simultaneously without altering embryo development to the blastocyst stage. The results provide valuable insights into the optimization of gene editing protocols for different models, opening new avenues for research and applications in this field. • Oocyte electroporation is an efficient method for generating single, double, and multiple knockout porcine embryos. • Electroporation does not interfere with early embryonic development. • Electroporation offers the potential to edit multiple genes simultaneously in a single step. [ABSTRACT FROM AUTHOR]

Background and Objectives: The influenza A(H1N1) virus is known for large outbreaks, epidemics and pandemics worldwide owing to its genome plasticity which evolves constantly. In the year 2015 and then in 2017, India witnessed an upsurge in cases. Materials and Methods: The study was carried out in this period (2015-2017) with samples from 5 states across north India. The hemagglutinin 1 (HA1) and non-structural 1 (NS1) gene segments of the viral genome were characterised by phylogenetic analysis, selection pressure analysis, prediction of potential glycosylation sites and phylodynamic analysis of the study strains. Results: The study strains belonged to genogroup 6B. A total of 12 mutations were observed, half of which were located on the key receptor binding region of the HA1 protein. Established virulence markers D222G, S183P were observed in 2017 samples. Acquisition of an extra glycosylation site was observed in few strains from 2017 and 2016. Selection pressure analysis found the average dN/dS (v) ratio of 0.2106 and few codon sites in particular showed significant evidence of being under negative selection. Conclusion: The genogroup 6B continues to be the dominant circulating strain in Indian subcontinent region however the presence of pathogenic mutations in the 2017 strains from north India underlines the importance of continued molecular surveillance. [ABSTRACT FROM AUTHOR]

Swine are regarded as "intermediate hosts" or "mixing vessels" of influenza viruses, capable of generating strains with pandemic potential. From 2020 to 2021, we conducted surveillance on swine H1N2 influenza (swH1N2) viruses in swine farms located in Guangdong, Yunnan, and Guizhou provinces in southern China, as well as Henan and Shandong provinces in northern China. We systematically analyzed the evolution and pathogenicity of swH1N2 isolates, and characterized their replication and transmission abilities. The isolated viruses are quadruple reassortant H1N2 viruses containing genes from pdm/09 H1N1 (PB2, PB1, PA and NP genes), triple-reassortant swine (NS gene), Eurasian Avian-like (HA and M genes), and recent human H3N2 (NA gene) lineages. The NA, PB2, and NP of SW/188/20 and SW/198/20 show high gene similarities to A/Guangdong/Yue Fang277/2017 (H3N2). The HA gene of swH1N2 exhibits a high evolutionary rate. The five swH1N2 isolates replicate efficiently in human, canine, and swine cells, as well as in the turbinate, trachea, and lungs of mice. A/swine/Shandong/198/2020 strain efficiently replicates in the respiratory tract of pigs and effectively transmitted among them. Collectively, these current swH1N2 viruses possess zoonotic potential, highlighting the need for strengthened surveillance of swH1N2 viruses. [ABSTRACT FROM AUTHOR]

Porcine respiratory coronavirus (PRCoV), porcine reproductive and respiratory syndrome virus (PRRSV), swine influenza virus (SIV), and pseudorabies virus (PRV) are significant viruses causing respiratory diseases in pigs. Sick pigs exhibit similar clinical symptoms such as fever, cough, runny nose, and dyspnea, making it very difficult to accurately differentially diagnose these diseases on site. In this study, a quadruplex one-step reverse-transcription real-time quantitative PCR (RT-qPCR) for the detection of PRCoV, PRRSV, SIV, and PRV was established. The assay showed strong specificity, high sensitivity, and good repeatability. It could detect only PRCoV, PRRSV, SIV, and PRV, without cross-reactions with TGEV, PEDV, PRoV, ASFV, FMDV, PCV2, PDCoV, and CSFV. The limits of detection (LODs) for PRCoV, PRRSV, SIV, and PRV were 129.594, 133.205, 139.791, and 136.600 copies/reaction, respectively. The intra-assay and inter-assay coefficients of variation (CVs) ranged from 0.29% to 1.89%. The established quadruplex RT-qPCR was used to test 4909 clinical specimens, which were collected in Guangxi Province, China, from July 2022 to September 2023. PRCoV, PRRSV, SIV, and PRV showed positivity rates of 1.36%, 10.17%, 4.87%, and 0.84%, respectively. In addition, the previously reported RT-qPCR was also used to test these specimens, and the agreement between these methods was higher than 99.43%. The established quadruplex RT-qPCR can accurately detect these four porcine respiratory viruses simultaneously, providing an accurate and reliable detection technique for clinical diagnosis. [ABSTRACT FROM AUTHOR]

This article explores the intersection between infectious diseases and exploration history. It discusses how encounters during exploration often lead to the spread of diseases, which can have a significant impact on new environments. The article also highlights the mythology and lore surrounding the role of disease in colonization and the shaping of exploration activities. It emphasizes that knowledge about exploration and disease is deeply political and can be used to gain advantages in various aspects of society. The article concludes by presenting three articles that delve into the relationship between exploration history and disease, including topics such as disease mapping in the Spanish-colonial Caribbean, the impact of disease on colonization in Papua New Guinea, and European perceptions of Indigenous health in the Americas. [Extracted from the article]

Orf virus (ORFV) is a large DNA virus that can harbor and efficiently deliver viral antigens in swine. Here we used ORFV as a vector platform to deliver chimeric hemagglutinins (HA) of Influenza A virus of swine (IAV-S). Vaccine development against IAV-S faces limitations posed by strain-specific immunity and the antigenic diversity of the IAV-S strains circulating in the field. A promising alternative aiming at re-directing immune responses on conserved epitopes of the stalk segment of the hemagglutinin (HA2) has recently emerged. Sequential immunization with chimeric HAs comprising the same stalk but distinct exotic head domains can potentially induce cross-reactive immune responses against conserved epitopes of the HA2 while breaking the immunodominance of the head domain (HA1). Here, we generated two recombinant ORFVs expressing chimeric HAs encoding the stalk region of a contemporary H1N1 IAV-S strain and exotic heads derived from either H6 or H8 subtypes, ORFVD121cH6/1 and ORFVD121cH8/1, respectively. The resulting recombinant viruses were able to express the heterologous protein in vitro. Further, the immunogenicity and cross-protection of these vaccine candidates were assessed in swine after sequential intramuscular immunization with OV-cH6/1 and OV-cH8/1, and subsequent challenge with divergent IAV-S strains. Humoral responses showed that vaccinated piglets presented increasing IgG responses in sera. Additionally, cross-reactive IgG and IgA antibody responses elicited by immunization were detected in sera and bronchoalveolar lavage (BAL), respectively, by ELISA against different viral clades and a diverse range of contemporary H1N1 IAV-S strains, indicating induction of humoral and mucosal immunity in vaccinated animals. Importantly, viral shedding was reduced in nasal swabs from vaccinated piglets after intranasal challenge with either Oh07 (gamma clade) or Ca09 (npdm clade) IAV-S strains. These results demonstrated the efficiency of ORFV-based vectors in delivering chimeric IAV-S HA-based vaccine candidates and underline the potential use of chimeric-HAs for prevention and control of influenza in swine. [ABSTRACT FROM AUTHOR]

Background: Influenza and corona viruses generate vaccine preventable diseases and have pandemic potential, frequently dramatic. A co-infection with these viruses, may be a new worldwide threat, researchers name it flurona. The aim of our study is to assess flu and COVID-19 Romanian vaccination for 2022–2023 season and the factor associated with higher odds to receive flu and COVID-19 vaccine. Methods: An analytical cross-sectional observational survey was conducted in the general population; a self-administered questionnaire was used. Results: 1056 responders were analyzed, mean age 32.08 ±13.36 years (limits:18–76), majority, 880 (83.33%), from urban areas, 608 (57.58%), high school graduated, 400 (37.88%) parents. More than half of the responders were healthcare workers, 582 (55.11%), also considered study population. In the study group, 796 (73.37%) responders consider flurona vaccination useful; and 872 (82.57%) responders consider that no sanctions are needed for not flurona vaccinating. In the 2022–2023 season, 162 (15.34%) responders vaccinated against the flu and 300 (28.41%) against COVID-19. The factor associated with higher odds to receive flu and COVID-19 vaccine was the habit of flu vaccination: for flu (OR = 58.43; 95% CI: (34.95–97.67)) and for COVID-19 (OR = 1.67; 95% CI: (1.21–2.31)). Other factors such as having university degree (OR = 1.46; 95% CI: (1.08–1.98)) and being a healthcare worker, (OR = 1.41; 95% CI: (1.07–1.87)) were influencing factors only for adult COVID-19 vaccination in the 2022–2023 season. In the parents' group, in 2022–2023 season, only 48 (12%) vaccinated their children against the flu and 68 (17%) against COVID-19, mostly parents that vaccinated themselves, p<0.001. In the 2022–2023 season, there were only 82 (7.65%) responders vaccinated against both diseases. Logistic regression analysis showed that no factor analyzed influenced the flurona vaccinated parent's decision to vaccinate their children for flu and for COVID-19. Conclusions: In the season 2022–2023, in Romania, the vaccination against flu and COVOD-19 is low, in adults and children as well. More efforts must be done to increase flurona vaccination, public health educational programs are strongly needed. Children, that are at greater risk when co-infecting with these viruses, must be vaccinated, school vaccination programs should be considered. [ABSTRACT FROM AUTHOR]

In this paper, we explore what the travel restrictions during the COVID-19 pandemic reveal about the changing geographies of mobilities and the making of homo sacer, the latter constituted through differentiated control of mobilities. Implemented to protect U.S. public health, travel restrictions imposed on travelers from Mainland China during the early days of the pandemic exemplify how sovereign power that declares a state of emergency and creates bare life can be readily applied to groups of people who previously had privileged access to global mobility. In this sense, bare life does not refer to fixed and disadvantaged social categories but is rather contingently and contextually constituted, through the works of hybrid sovereign regimes. At the same time, however, these travelers are not reduced to a state of zero-agency but reside within a liminal space between soft and hard cosmopolitanisms, as they can still deploy agency and cosmopolitan capital to achieve certain degrees of mobility. By examining how Chinese travelers navigated various travel restrictions and the constantly changing policies to travel to the U.S., this paper explores new spaces of exception and forms of bare life, and argues that homo sacer is dynamically, relationally and recursively constructed, both through apparatus of control and the agency of travelers. [ABSTRACT FROM AUTHOR]

Characterizing the mutational diversity of viruses can shed light on both intra-host and between-host evolutionary processes. In this study, we analyzed the transcriptome profiles of five different strains of Influenza A virus H1N1 isolated from humans, ducks, and pigs. We detected positive selection that led to the evolution and fixation of virus variants at the intra-host level. Among the strains studied, A/mallard/Balkhash/6304/2014 was the most affected by intra-host dynamics, with 143 substitutions, while A/Puerto Rico/8/34 (PR8) had the least, with only one substitution. A/California/04/09 had the highest frequency of distribution in the HA epitope sites. We also detected amino acid substitutions in immunodominant antigenic regions of A/WSN/1933, mallard, and swine influenza strains. We detected a total of 19 shared substitutions across both the inter-host and intra-host levels. The sequences of the different strains showed different patterns of gene expression. Phylogenetic trees constructed based on the HA and NA segments of the 26 GenBank isolates showed incongruences with other phylogenetic trees based on other IAV segments. We also identified amino acid changes in critical regions of the studied isolates, which could provide valuable information on the contingency of novel recombinants with different morphogenesis, infectivity, and behavior against antivirals. Our results show that influenza A viruses (IAVs) could potentially adapt more efficiently within their host organisms, mostly in wild birds. This underlines the importance of certain population characteristics, such as the elimination of genetic bottlenecks, as a means to expand their ability to infect new hosts. [ABSTRACT FROM AUTHOR]

The increased detection of H3 C-IVA (1990.4.a) clade influenza A viruses (IAVs) in US swine in 2019 was associated with a reassortment event to acquire an H1N1pdm09 lineage nucleoprotein (pdmNP) gene, replacing a TRIG lineage NP (trigNP). We hypothesized that acquiring the pdmNP conferred a selective advantage over prior circulating H3 viruses with a trigNP. To investigate the role of NP reassortment in transmission, we identified two contemporary 1990.4.a representative strains (NC/19 and MN/18) with different evolutionary origins of the NP gene. A reverse genetics system was used to generate wild-type (wt) strains and swap the pdm and TRIG lineage NP genes, generating four viruses: wtNC/19-pdmNP, NC/19-trigNP, wtMN/18-trigNP, and MN/18-pdmNP. The pathogenicity and transmission of the four viruses were compared in pigs. All four viruses infected 10 primary pigs and transmitted to five indirect contact pigs per group. Pigs infected via contact with MN/18-pdmNP shed virus 2 days earlier than pigs infected with wtMN/18-trigNP. The inverse did not occur for wtNC/19-pdmNP and NC/19-trigNP. This suggests that pdmNP reassortment resulted in a combination of genes that improved transmission efficiency when paired with the 1990.4.a hemagglutinin (HA). This is likely a multigenic trait, as replacing the trigNP gene did not diminish the transmission of a wild-type IAV in swine. This study demonstrates how reassortment and evolutionary change of internal genes can result in more transmissible viruses that influence HA clade detection frequency. Thus, rapidly identifying novel reassortants paired with dominant hemagglutinin/neuraminidase may improve the prediction of strains to include in vaccines. [ABSTRACT FROM AUTHOR]

Lung infections in Influenza-Like Illness (ILI) are triggered by a variety of respiratory viruses. All human pandemics have been caused by the members of two major virus families, namely Orthomyxoviridae (influenza A viruses (IAVs); subtypes H1N1, H2N2, and H3N2) and Coronaviridae (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2). These viruses acquired some adaptive changes in a known intermediate host including domestic birds (IAVs) or unknown intermediate host (SARS-CoV-2) following transmission from their natural reservoirs (e.g. migratory birds or bats, respectively). Verily, these acquired adaptive substitutions facilitated crossing species barriers by these viruses to infect humans in a phenomenon that is known as zoonosis. Besides, these adaptive substitutions aided the variant strain to transmit horizontally to other contact non-human animal species including pets and wild animals (zooanthroponosis). Herein we discuss the main zoonotic and reverse-zoonosis events that occurred during the last two pandemics of influenza A/H1N1 and SARS-CoV-2. We also highlight the impact of interspecies transmission of these pandemic viruses on virus evolution and possible prophylactic and therapeutic interventions. Based on information available and presented in this review article, it is important to close monitoring viral zoonosis and viral reverse zoonosis of pandemic strains within a One-Health and One-World approach to mitigate their unforeseen risks, such as virus evolution and resistance to limited prophylactic and therapeutic interventions. [ABSTRACT FROM AUTHOR]

• Swine flu is important in pigs and difficult to control due to high heterogeneity of isolates. • An experimental flu vaccine based on the conserved M2e epitope was produced and tested in pigs. • Induction of humoral IgG M2e antibodies was observed. • Vaccinated pigs were not protected upon challenge. • A vaccine solely based on M2e alone may not be sufficient to induce protection in pigs. Swine flu is a common disease problem in North American pig populations and swine influenza A viruses (IAV) are extremely diverse and the lack of cross protection between heterologous strains is impacting vaccine efficacy in the field. The objective of this study was to design and test a novel swine flu vaccine targeting the M2 ectodomain (M2e) of IAV, a highly conserved region within the IAV proteome. In brief, an M2e peptide was designed to match the predominant swine IAV M2 sequence based on global analysis of sequences from pigs and humans. The resulting sequence was used to synthesize the M2e peptide coupled to a carrier protein. The final vaccine concentration was 200 µg per dose, and a commercial, microemulsion-based aqueous adjuvant was added. Nine 3-week-old IAV negative piglets were randomly assigned to three groups and rooms including non-vaccinated pigs (NEG-CONTROLs) and vaccinated pigs using the intramuscular (M2e-IM) or the intranasal route (M2e-IN). Vaccinations were done at weaning and again at 2 weeks later. An in-house enzyme-linked immunosorbent assay (ELISA) was developed and validated to study the M2e IgG antibody response and demonstrated M2e-IM pigs had a higher systemic antibody response compared to M2e-IN pigs. Subsequently, an IAV challenge study was conducted. The results indicated that M2e-IM vaccinated pigs were not protected from H1N1 (US pandemic clade, global clade 1A.3.3.2) challenge despite having a strong humoral anti-M2e immune response. In conclusion, while the experimental IAV vaccine was able to induce anti-M2e antibodies, when challenged with H1N1, the vaccinated pigs were not protected, perhaps indicating that reactivity to the M2e antigen alone is not sufficient to reduce clinical signs, lesions or shedding associated with experimental IAV challenge. [ABSTRACT FROM AUTHOR]

Influenza pandemic with H1N1 (H1N1pdms) causes severe lung damage and "cytokine storm," leading to higher mortality and global health emergencies in humans and animals. Explaining host antiviral molecular mechanisms in response to H1N1pdms is important for the development of novel therapies. In this study, we organised and analysed multimicroarray data for mouse lungs infected with different H1N1pdm and nonpandemic H1N1 strains. We found that H1N1pdms infection resulted in a large proportion of differentially expressed genes (DEGs) in the infected lungs compared with normal lungs, and the number of DEGs increased markedly with the time of infection. In addition, we found that different H1N1pdm strains induced similarly innate immune responses and the identified DEGs during H1N1pdms infection were functionally concentrated in defence response to virus, cytokine-mediated signalling pathway, regulation of innate immune response, and response to interferon. Moreover, comparing with nonpandemic H1N1, we identified ten distinct DEGs (AREG, CXCL13, GATM, GPR171, IFI35, IFI47, IFIT3, ORM1, RETNLA, and UBD), which were enriched in immune response and cell surface receptor signalling pathway as well as interacted with immune response-related dysregulated genes during H1N1pdms. Our discoveries will provide comprehensive insights into host responding to pandemic with influenza H1N1 and find broad-spectrum effective treatment. [ABSTRACT FROM AUTHOR]

Background: Cross-species transmission of zoonotic IAVs to humans is potentially widespread and lethal, posing a great threat to human health, and their cross-species transmission mechanism has attracted much attention. miRNAs have been shown to be involved in the regulation of IAVs infection and immunity, however, few studies have focused on the molecular mechanisms underlying miRNAs and mRNAs expression after IAVs cross-species infection. Methods: We used tree shrews, a close relative of primates, as a model and used RNA-Seq and bioinformatics tools to analyze the expression profiles of DEMs and DEGs in the nasal turbinate tissue at different time points after the newly emerged swine influenza A virus SW2783 cross-species infection with tree shrews, and miRNA-mRNA interaction maps were constructed and verified by RT-qPCR, miRNA transfection and luciferase reporter assay. Results: 14 DEMs were screened based on functional analysis and interaction map, miR-760-3p, miR-449b-2, miR-30e-3p, and miR-429 were involved in the signal transduction process of replication and proliferation after infection, miR-324-3p, miR-1301-1, miR-103-1, miR-134-5p, miR-29a, miR-31, miR-16b, miR-34a, and miR-125b participate in negative feedback regulation of genes related to the immune function of the body to activate the antiviral immune response, and miR-106b-3p may be related to the cross-species infection potential of SW2783, and the expression level of these miRNAs varies in different days after infection. Conclusions: The miRNA regulatory networks were constructed and 14 DEMs were identified, some of them can affect the replication and proliferation of viruses by regulating signal transduction, while others can play an antiviral role by regulating the immune response. It indicates that abnormal expression of miRNAs plays a crucial role in the regulation of cross-species IAVs infection, which lays a solid foundation for further exploration of the molecular regulatory mechanism of miRNAs in IAVs cross-species infection and anti-influenza virus targets. [ABSTRACT FROM AUTHOR]

Swine flu, caused by the H1N1 influenza virus, is a subtype of influenza A that affects both the upper and lower respiratory tracts. It is primarily found in pigs and can be transmitted to humans through genetic variations in the virus. The 1918 Spanish flu pandemic resulted in the deaths of 50 to 100 million individuals. In 2009, the pandemic affected 178 countries, resulting in an estimated 43 to 89 million cases and 1799 deaths. The pathophysiology of H1N1 involves inflammation of the respiratory tract, with an incubation period of 1 to 4 days and a contagious period lasting 5 to 7 days. The signs and symptoms of swine flu include cough, sore throat, fever, myalgia, congestion, headache, rhinorrhoea, dizziness, sneezing, loss of appetite, fatigue, abdominal pain, shortness of breath, and in rare cases, vomiting and diarrhoea. The most common cause of death is respiratory failure, and neurological symptoms can occur due to high fever. To diagnose swine flu, various tests such as haematological, biochemical, and microbiological tests are conducted, including the collection of nasal or oral swabs for reverse transcriptase polymerase chain reaction (RT-PCR). Prevention and control measures include managing swine flu in pigs through herd management, hygiene practices, and vaccination. Treatment options vary based on the severity of the case. Mild to moderate cases can be managed with rest, antipyretics, NSAIDs, antihistamines, and oral rehydration therapy. Severe cases may require intravenous hydration, antibiotics for bacterial infections, antiviral therapy, and respiratory support. [ABSTRACT FROM AUTHOR]