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We isolated highly pathogenic avian influenza (HPAI) H5N5 and H5N1 viruses from crows in Hokkaido, Japan, during winter 2023-24. They shared genetic similarity with HPAI H5N5 viruses from northern Europe but differed from those in Asia. Continuous monitoring and rapid information sharing between countries are needed to prevent HPAI virus transmission.
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Corvos , Virus da Influenza A Subtipo H5N1 , Influenza Aviária , Filogenia , Animais , Influenza Aviária/virologia , Influenza Aviária/epidemiologia , Japão/epidemiologia , Virus da Influenza A Subtipo H5N1/genética , Virus da Influenza A Subtipo H5N1/patogenicidade , Virus da Influenza A Subtipo H5N1/classificação , Virus da Influenza A Subtipo H5N1/isolamento & purificação , Corvos/virologia , Vírus da Influenza A/genética , Vírus da Influenza A/classificaçãoRESUMO
The H9N2 avian influenza virus (AIV) is spreading worldwide. Presence of H9N2 virus tends to increase the chances of infection with other pathogens which can lead to more serious economic losses. In a previous study, a regulated delayed lysis Salmonella vector was used to deliver a DNA vaccine named pYL233 encoding M1 protein, mosaic HA protein and chicken GM-CSF adjuvant. To further increase its efficiency, chitosan as a natural adjuvant was applied in this study. The purified plasmid pYL233 was coated with chitosan to form a DNA containing nanoparticles (named CS233) by ionic gel method and immunized by intranasal boost immunization in birds primed by oral administration with Salmonella strain. The CS233 DNA nanoparticle has a particle size of about 150 nm, with an encapsulation efficiency of 93.2 ± 0.12 % which protected the DNA plasmid from DNase I digestion and could be stable for a period of time at 37°. After intranasal boost immunization, the CS233 immunized chickens elicited higher antibody response, elevated CD4+ T cells and CD8+ T cells activation and increased T-lymphocyte proliferation, as well as increased productions of IL-4 and IFN-γ. After challenge, chickens immunized with CS233 resulted in the lowest levels of pulmonary virus titer and viral shedding as compared to the other challenge groups. The results showed that the combination of intranasal immunization with chitosan-coated DNA vaccine and oral immunization with regulatory delayed lytic Salmonella strain could enhance the immune response and able to provide protection against H9N2 challenge.
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Since 2022, three human cases of a novel H3N8 avian influenza virus infection have been reported in three provinces in China. Specific vaccines are important means of preparing for the potential influenza pandemic. Thus, H3N8 viruses [A/Henan/cnic410/2022 (HN410) and A/Changsha/1000/2022(CS1000)] were isolated from the infected patients as prototype viruses to develop candidate vaccine viruses (CVVs) using the reverse genetics (RG) technology. Five reassortant viruses with different HA and NA combinations were constructed based on the two viruses to get a high-yield and safe CVV. The results showed that all viruses had similar antigenicity but different growth characteristics. Reassortant viruses carrying NA from CS1000 exhibited better growth ability and NA enzyme activity than the ones carrying HN410 NA. Furthermore, the NA gene of CS1000 had one more potential N-glycosylation site at position 46 compared with HN410. The substitution of position 46 showed that adding or removing N-glycosylation sites to different reassortant viruses had different effects on growth ability. A reassortant virus carrying HN410 HA and CS1000 NA with high growth ability was selected as a CVV, which met the requirements for a CVV. These data suggest that different surface gene combinations and the presence or absence of potential N-glycosylation sites on position 46 in the NA gene affect the growth characteristics of H3N8 CVVs.
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Highly pathogenic avian influenza (HPAI) poses a significant threat to animal and public health, with outbreaks occurring globally. HPAI poses significant challenges due to its high mortality rate and public health concerns, with outbreaks spreading globally since the emergence of the H5N1 virus in 2003. In Japan, HPAI outbreaks have been particularly prevalent during autumn and winter seasons, with the 2022-2023 winter experiencing the most severe outbreak to date. However, limited research has directly examined the association between HPAI outbreaks and weather conditions in Japan. Here we show that specific weather conditions are associated with an increased risk of HPAI outbreaks on poultry farms in Japan. By analyzing databases of HPAI cases and meteorological data from 2020-2023, we found that higher average air temperatures two to three weeks prior, lower average wind speeds four weeks prior, and longer sunlight hours two and four weeks prior to outbreaks were significantly associated with increased risk of HPAI outbreaks in Japan. These results suggest that weather may influence environmental survival and transmission of the virus, as well as patterns of wild bird movement that could seed new outbreaks. These findings enhance our understanding of the factors influencing HPAI transmission dynamics and highlight the importance of integrating weather forecasts into disease surveillance and prevention strategies.
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Surveillance data from wildlife and poultry was used to describe the spread of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b in British Columbia (B.C.) and the Yukon, Canada from September 2022 - June 2023 compared to the first 'wave' of the outbreak in this region, which occurred April - August 2022, after the initial viral introduction. Although the number of HPAI-positive poultry farms and wildlife samples was greater in 'Wave 2', cases were more tightly clustered in southwestern B.C. and the most commonly affected species differed, likely due to an influx of overwintering waterfowl in the area. Eight HPAI genetic clusters, representing seven genotypes and two inter-continental viral incursions, were detected, with significant variation in the relative abundance of each cluster between the waves. Phylogenetic data suggests multiple spillover events from wild birds to poultry and mammals but could not rule out transmission among farms and among mammals.
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The COVID-19 pandemic caused by SARS-CoV-2 has had a persistent and significant impact on global public health for 4 years. Recently, there has been a resurgence of seasonal influenza transmission worldwide. The co-circulation of SARS-CoV-2 and seasonal influenza viruses results in a dual burden on communities. Additionally, the pandemic potential of zoonotic influenza viruses, such as avian Influenza A/H5N1 and A/H7N9, remains a concern. Therefore, a combined vaccine against all these respiratory diseases is in urgent need. mRNA vaccines, with their superior efficacy, speed in development, flexibility, and cost-effectiveness, offer a promising solution for such infectious diseases and potential future pandemics. In this study, we present FLUCOV-10, a novel 10-valent mRNA vaccine created from our proven platform. This vaccine encodes hemagglutinin (HA) proteins from four seasonal influenza viruses and two avian influenza viruses with pandemic potential, as well as spike proteins from four SARS-CoV-2 variants. A two-dose immunization with the FLUCOV-10 elicited robust immune responses in mice, producing IgG antibodies, neutralizing antibodies, and antigen-specific cellular immune responses against all the vaccine-matched viruses of influenza and SARS-CoV-2. Remarkably, the FLUCOV-10 immunization provided complete protection in mouse models against both homologous and heterologous strains of influenza and SARS-CoV-2. These results highlight the potential of FLUCOV-10 as an effective vaccine candidate for the prevention of influenza and COVID-19.IMPORTANCEAmidst the ongoing and emerging respiratory viral threats, particularly the concurrent and sequential spread of SARS-CoV-2 and influenza, our research introduces FLUCOV-10. This novel mRNA-based combination vaccine, designed to counteract both influenza and COVID-19, by incorporating genes for surface glycoproteins from various influenza viruses and SARS-CoV-2 variants. This combination vaccine was highly effective in preclinical trials, generating strong immune responses and ensuring protection against both matching and heterologous strains of influenza viruses and SARS-CoV-2. FLUCOV-10 represents a significant step forward in our ability to address respiratory viral threats, showcasing potential as a singular, adaptable vaccine solution for global health challenges.
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Avian influenza virus has been long considered the main threat for a future pandemic. Among the possible avian influenza virus subtypes, A(H5N1) clade 2.3.4.4b is becoming enzootic in mammals, representing an alarming step towards a pandemic. In particular, genotype B3.13 has recently caused an outbreak in US dairy cattle. Since pandemic preparedness is largely based on the availability of prepandemic candidate vaccine viruses, in this review we will summarize the current status of the enzootics, and challenges for H5 vaccine manufacturing and delivery.
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Virus da Influenza A Subtipo H5N1 , Vacinas contra Influenza , Influenza Aviária , Animais , Vacinas contra Influenza/imunologia , Humanos , Virus da Influenza A Subtipo H5N1/imunologia , Virus da Influenza A Subtipo H5N1/genética , Influenza Aviária/prevenção & controle , Influenza Aviária/virologia , Influenza Aviária/epidemiologia , Influenza Humana/prevenção & controle , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Influenza Humana/virologia , Aves/virologia , Pandemias/prevenção & controleRESUMO
This study reports the synthesis and analysis of biologically active acylthiourea compounds (1 and 2) with a cyclohexyl moiety. The compounds were characterized using UV-Visible, FT-IR, 1H/13C NMR, and elemental analysis. The crystal structure of 2 was solved, revealing intra- and inter-molecular hydrogen bonds. Density functional theory (DFT) calculations provided insights into chemical reactivity and non-covalent interactions. Cytotoxicity assays showed the cyclohexyl group enhanced the activity of compound 2 compared to compound 1. Epoxide hydrolase 1 was predicted as the enzyme target for both compounds. We modeled the structure of epoxide hydrolase 1 and performed molecular dynamics simulation and docking studies. Additionally, in silico docking with SARS-CoV-2 main protease, human ACE2, and avian influenza H5N1 hemagglutinin indicated strong binding potential. This integrated approach improves our understanding of the biological potential of acylthiourea derivatives.
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Avian influenza remains a global public health concern for its well-known point mutation and genomic segment reassortment, through which plenty of serum serotypes are generated to escape existing immune protection in animal and human populations. Some occasional cases of human infection of avian influenza viruses (AIVs) since 2020 posed a potential pandemic risk through human-to-human transmission. Both east-west and north-south migratory birds fly through and linger in the Hebei Province of China as a stopover habitat, providing an opportunity for imported AIVs to infect the local poultry and for viral gene reassortment to generate novel stains. In this study, we collected more than 6,000 environmental samples (mostly feces) in Hebei Province from 2021 to 2023. Samples were screened using real-time RT-PCR, and virus isolation was performed using the chick embryo culture method. We identified 10 AIV isolates, including a novel reassortant H3N3 isolate. Sequencing analysis revealed these AIVs to be highly homologous to those isolated in the Yellow River Basin. Our findings supported that AIVs keep evolving to generate new isolates, necessitating a continuous risk assessment of local avian influenza in wild waterfowl in Hebei, China.
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During poultry immunization, antibiotics are typically added to inactivated oil-adjuvant avian influenza (AI) vaccines. Here, we evaluated the effects of adding ceftiofur, a third-generation cephalosporin, to an AI vaccine on vaccine stability and structure and on chick growth, immune efficacy, blood concentrations, biochemical and immunological indices, and gut microbiota. The results demonstrated that neither aqueous ceftiofur sodium nor ceftiofur hydrochloride oil emulsion formed a stable mixture with the vaccine. Adding ceftiofur formulations, particularly ceftiofur hydrochloride, at >4% significantly destabilized the vaccine's water-in-oil structures. Adding ceftiofur also increased vaccine malabsorption at the injection site; specifically, adding ceftiofur hydrochloride reduced H5N8 and H7N9 antibody titers after the first immunization (P < 0.05) and H7N9 antibody titers after the second immunization (P < 0.01). Serum drug concentrations did not differ significantly between the groups with ceftiofur sodium and hydrochloride addition. Ceftiofur addition increased postvaccination chick weight loss; compared with the vaccine alone, ceftiofur sodium-vaccine mixture increased chick weight significantly (P < 0.05). Ceftiofur addition also increased stress indices and reduced antioxidant capacity significantly (P < 0.05 or P < 0.01). Vaccination-related immune stress reduced gut microbiota diversity in chicks; ceftiofur addition reversed this change. AI vaccine immunization significantly reduced the relative abundance of Lactobacillus and Muribaculaceae but significantly increased that of Bacteroides and Eubacterium coprostanoligenes group. Ceftiofur addition restored the gut microbiota structure; in particular, ceftiofur hydrochloride addition significantly increased the abundance of the harmful gut microbes Escherichia-Shigella and Enterococcus, whereas ceftiofur sodium addition significantly reduced it. The changes in gut microbiota led to alterations in metabolic pathways related to membrane transport, amino acids, and carbohydrates. In conclusion, adding ceftiofur to the AI vaccine had positive effects on chick growth and gut microbiota modulation; however, different antibiotic concentrations and formulations may disrupt vaccine structure, possibly affecting vaccine safety and immunization efficacy. Thus, the addition of antibiotics to oil-adjuvant vaccines is associated with a risk of immunization failure and should be applied to poultry with caution.
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In July 2022, an outbreak of highly pathogenic avian influenza A(H5N1) virus clade 2.3.4.4b occurred among migratory birds at Qinghai Lake in China. The virus circulated in June, and reassortants emerged after its introduction into the area. Surveillance in 2023 showed that the virus did not establish a stable presence in wild waterfowl.
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Avian influenza virus (AIV) subtype H9N2 has significantly threatened the poultry business in recent years by having become the predominant subtype in flocks of chickens, ducks, and pigeons. In addition, the public health aspects of H9N2 AIV pose a significant threat to humans. Early and rapid diagnosis of H9N2 AIV is therefore of great importance. In this study, a new method for the detection of H9N2 AIV based on fluorescence intensity was successfully established using CRISPR/Cas13a technology. The Cas13a protein was first expressed in a prokaryotic system and purified using nickel ion affinity chromatography, resulting in a high-purity Cas13a protein. The best RPA (recombinase polymerase amplification) primer pairs and crRNA were designed and screened, successfully constructing the detection of H9N2 AIV based on CRISPR/Cas13a technology. Optimal concentration of Cas13a and crRNA was determined to optimize the constructed assay. The sensitivity of the optimized detection system is excellent, with a minimum detection limit of 10° copies/µL and didn't react with other avian susceptible viruses, with excellent specificity. The detection method provides the basis for the field detection of the H9N2 AIV.
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There is growing concern that the severe respiratory disease in birds (avian influenza or 'bird flu') caused by the H5N1 influenza virus, might potentially spread more widely to humans and cause a pandemic. Here we discuss clinical issues related to human infections by the highly pathogenic H5N1 subtype of the avian influenza A virus and make a clinical comparison with recent information obtained from studies of SARS-CoV-2 infection. Firstly, we consider the potential increase in cardiovascular events in humans infected with the H5N1 virus. Like SARS-CoV-2 infection, H5N1 infection may result in endothelial dysfunction and the associated procoagulant and prothrombotic state, and via this mechanism, the infection can potentially increase cardiovascular morbidity, especially in vulnerable individuals with pre-existing cardiovascular disease. Secondly, we discuss the potential beneficial role of statin use, both in the prophylaxis and the treatment of individuals with influenza A(H5N1), as was found favorable for the treatment of COVID-19 caused by SARS-CoV-2 infection.
There is a concern that avian influenza caused by the highly pathogenic avian influenza A(H5N1) virus might potentially spread more widely to humans and result in a pandemicH5N1 infection may result in endothelial dysfunction and via this mechanism, it can potentially increase cardiovascular morbidity and mortality as has occurred with SARS-CoV-2 infection.There is a potential advantage of the use of statins to reduce cardiovascular morbidity and mortality in patients with avian influenza A(H5N1), as has been found in patients suffering from COVID-19.
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COVID-19 , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Virus da Influenza A Subtipo H5N1 , Influenza Humana , Humanos , Virus da Influenza A Subtipo H5N1/efeitos dos fármacos , Influenza Humana/prevenção & controle , Influenza Humana/epidemiologia , COVID-19/prevenção & controle , COVID-19/complicações , COVID-19/epidemiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/epidemiologia , Animais , SARS-CoV-2 , Influenza Aviária/epidemiologia , Aves , Pandemias , Tratamento Farmacológico da COVID-19RESUMO
The recent detection of highly pathogenic avian influenza (HPAI) H5N1 in dairy cattle is a cross-species infection, underscoring the adaptability of the virus to infect mammals, particularly domestic ruminants across multiple farms. The outbreak has had a huge economic impact, including the depopulation of millions of hens. While current influenza surveillance indicates no unusual human influenza activity, the situation has raised public concerns due to the virus's zoonotic potential and its devastating impact on both avian and mammalian species. Most importantly, thorough surveillance and adherence to food safety measures to prevent potential human infections are top priorities.
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The prevalence of avian influenza viruses is commonly found to increase dramatically as birds are transported from farms to live bird markets. Viral transmission dynamics along marketing chains are, however, poorly understood. To address this gap, we implemented a controlled field experiment altering chicken supply to a live bird market in Chattogram, Bangladesh. Broilers and backyard chickens traded along altered (intervention) and conventional (control) marketing chains were tested for avian influenza viruses at different time points. Upon arrival at the live bird market, the odds of detecting avian influenza viruses did not differ between control and intervention groups. However, 12â¯h later, intervention group odds were lower, particularly for broilers, indicating that viral shedding in live bird markets resulted partly from infections occurring during transport and trade. Curtailing avian influenza virus prevalence in live bird markets requires mitigating risk in marketing chain nodes preceding chickens' delivery at live bird markets.
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Galinhas , Influenza Aviária , Doenças das Aves Domésticas , Animais , Influenza Aviária/epidemiologia , Influenza Aviária/virologia , Bangladesh/epidemiologia , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/epidemiologia , Doenças das Aves Domésticas/transmissão , Doenças das Aves Domésticas/prevenção & controle , Prevalência , Vírus da Influenza A/isolamento & purificação , Meios de Transporte , Criação de Animais Domésticos/métodos , Eliminação de Partículas Virais , Marketing , ComércioRESUMO
Highly pathogenic avian influenza (HPAI) is an important zoonotic disease. The study aims to identify farmer behaviour types to inform the design of behaviour change programmes for mitigating the transmission of HPAI. Therefore, the study utilised multivariate statistical analysis for gaining a better understanding of the relationships among farmers' 30 biosecurity behaviours, the risk of HPAI infection, and distinct features of commercial broiler farmers, which is different from using simple and few binary biosecurity measures. Convenience sampling was used to collect data from 303 Taiwan's farmers among which 40 farmers (13.2%) self-reported having had a HPAI outbreak in the study year while 16 farmers (5.3%) self-reported having had a HPAI outbreak in the past two years. Using categorical principal components analysis and a two-stage cluster analysis, four farmer clusters were identified with distinct features: 1)'Reserved' (4.6%) tended to choose 'No idea' for answering specific questions about HPAI; 2)'Secure' (76.3%) had a higher biosecurity status than the other farms; 3) 'Jeopardised' (16.8%) had a lower biosecurity status than the other farms; 4) 'No-response' (2.3%) tended to skip specific questions about HPAI. The biosecurity status of the 'Reserved' and 'No-response' clusters was undetermined, placing these farms at risk of HPAI infection. Compared to the 'Secure' cluster, the 'Jeopardised' cluster exhibited higher odds of self-reported HPAI in the study year (OR: 2.61, 95% CI: 1.22-5.58) and in the past two years (OR: 4.28, 95% CI: 1.39-13.19). Additionally, the 'Jeopardised' cluster showed increased odds of HPAI recurrence (OR: 4.01, 95% CI: 1.41-11.43). Our study demonstrates that inadequate biosecurity practices can elevate the occurrence or recurrence of HPAI outbreaks. The findings underscore the importance of distinguishing between these clusters to accurately assess the risk of HPAI infection across farms. Furthermore, understanding farmers' behaviours can inform the development of strategies aimed at behaviour change among farmers.
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Background: In recent years, Vietnam has suffered multiple epizootics of influenza in poultry. Methods: From 10 January 2019 to 26 April 2021, we employed a One Health influenza surveillance approach at live bird markets (LBMs) and swine farms in Northern Vietnam. When the COVID-19 pandemic permitted, each month, field teams collected oral secretion samples from poultry and pigs, animal facility bioaerosol and fecal samples, and animal worker nasal washes at 4 LBMs and 5 swine farms across 5 sites. Initially samples were screened with molecular assays followed by culture in embryonated eggs (poultry swabs) or Madin-Darby canine kidney cells (human or swine swabs). Results: Many of the 3493 samples collected had either molecular or culture evidence for influenza A virus, including 314 (37.5%) of the 837 poultry oropharyngeal swabs, 144 (25.1%) of the 574 bioaerosol samples, 438 (34.9%) of the 1257 poultry fecal swab samples, and 16 (1.9%) of the 828 human nasal washes. Culturing poultry samples yielded 454 influenza A isolates, 83 of which were H5, and 70 (84.3%) of these were highly pathogenic. Additionally, a positive human sample had a H9N2 avian-like PB1 gene. In contrast, the prevalence of influenza A in the swine farms was much lower with only 6 (0.4%) of the 1700 total swine farm samples studied, having molecular evidence for influenza A virus. Conclusions: This study suggests that Vietnam's LBMs continue to harbor high prevalences of avian influenza A viruses, including many highly pathogenic H5N6 strains, which will continue to threaten poultry and humans.
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Avian influenza viruses (AIVs) have the potential to cause severe illness in wild birds, domestic poultry, and humans. The ongoing circulation of highly pathogenic avian influenza viruses (HPAIVs) has presented significant challenges to global poultry industry and public health in recent years. This study aimed to elucidate the circulation of HPAIVs during 2019 to 2023. Specifically, we assess the alarming global spread and continuous evolution of HPAIVs. Moreover, we discuss their transmission and prevention strategies to provide valuable references for future prevention and control measures against AIVs.