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A locally administered single-cycle #influenza #vaccine expressing a non-fusogenic stabilized #hemagglutinin stimulates strong T-cell and neutralizing #antibody #immunity

ABSTRACT Current influenza vaccination approaches protect against specific viral strains, but do not consistently induce broad and long-lasting protection to the diversity of circulating influenza viruses. Single-cycle viruses delivered to the respiratory tract may offer a promising solution as they safely express a diverse array of viral antigens by undergoing just one round of cell infection in their host and stimulate broadly protective resident memory T-cell responses in the lung. We have previously developed a vaccine candidate called S-FLU , which is limited to a single cycle of infection by inactivation of the hemagglutinin signal sequence and induces a broadly cross-reactive T-cell response and antibodies to neuraminidase, but fails to induce neutralizing antibodies to hemagglutinin after intranasal administration. This study describes the development of CLEARFLU , a derivative of S-FLU, which is designed to add a neutralizing antibody response to hemagglutinin. In contrast to ...

#Influenza at the #human - #animal #interface - #Summary and #risk #assessment, from 13 December 2024 to 20 January 202

New human cases {2}:  From 13 December 2024 to 20 January 2025, the detection of influenza A(H5) virus in five humans , influenza A( H9N2 ) virus in two humans , and influenza A( H10N3 ) virus in one human were reported officially. Additionally, five human cases of infection with influenza A(H5) viruses were detected.   Circulation of influenza viruses with zoonotic potential in animals :  High pathogenicity avian influenza (HPAI) events in poultry and non-poultry continue to be reported to the World Organisation for Animal Health (WOAH).{3} The Food and Agriculture Organization of the United Nations (FAO) also provides a global update on avian influenza viruses with pandemic potential.{4}   Risk assessment {5}:  Based on information available at the time of the risk assessment , the overall public health risk from currently known influenza viruses at the human-animal interface has not changed remains low . Sustained human to human transmission has not...

Avian #influenza #risk of #upsurge and regional spread through increased #poultry #trade before and during #Lunar New Year #festivities in #Asia

FAO calls for increased vigilance and preparedness for avian influenza (AI) during the traditional New Year festivities that will take place across Asia on the week of 27 January 2025 . In the past year, outbreaks of AI have continued to be reported in domestic poultry, wild birds and mammals in Asia . Several AI virus subtypes including H5N1, H5N2, H5N3, H5N5, H5N6, H5N8, H7N3, H7N6, H7N8, H7N9, H10N5 , and H3N2 are currently well-established in both wild and domestic bird populations in the region. In addition, subtype H5N1 subclade 2.3.4.4b continues to circulate in both wild and domestic birds worldwide. Highly pathogenic avian influenza (HPAI) can lead to heavy losses for the poultry industry, in particular to the livelihoods of vulnerable small-scale producers . Poultry trade and related activities play a key role in AI spread and amplification in domestic bird populations, including the trade of infected live poultry and their products, handling or slaughtering infected poultry,...

#UK, #Human case of avian #influenza #H5N1 detected in #England

UKHSA has confirmed a case of influenza A(H5N1) in a person in the West Midlands region. Bird-to-human transmission of avian influenza is rare and has previously occurred a small number of times in the UK . The person acquired the infection on a farm , where they had close and prolonged contact with a large number of infected birds. The risk to the wider public continues to be very low. The individual is currently well and was admitted to a High Consequence Infectious Disease (HCID) unit. The birds were infected with the DI.2 genotype , one of the viruses known to be circulating in birds in the UK this season. This is different to strains circulating among mammals and birds in the US. Although there has been no demonstrated human-to-human transmission despite extensive recent surveillance of influenza A(H5N1), UKHSA has been tracing all individuals who have been in contact with the confirmed case of avian influenza. Those at highest risk of exposure have been offered antiviral treatmen...

#Isolation and Characterization of #H1 Subtype #Swine #Influenza Viruses Recently Circulating in #China

Abstract Pigs serve as a mixing vessel for influenza viruses and can independently promote the emergence of pandemic strains in humans. During our surveillance of pig populations from 2021 to 2023 in China , 11 H1 subtype swine influenza viruses (SIVs) were isolated. All viruses were reassortants , possessing internal genes of identical origins ( PB2, PB1, PA, NP, M : pdm09/H1N1 origin, NS : North American triple reassortant origin). The H1N1 isolates were all the dominant G4 EA H1N1 viruses in China. Two H1N2 isolates carried early human pdm09/H1N1 HA genes, suggesting a possible pig-to-human transmission route. Mutations that dictate host range specificity were identified in all isolates, a phenomenon which may enhance the affinity to human receptors. These H1 subtype viruses effectively replicated both in vivo and in vitro without prior adaptation and exhibited different pathogenicity and growth characteristics. Some of the H1 viruses were even found to cause lethal infections in mi...

Improving #clinical #care of patients in #Nipah #outbreaks: moving beyond ‘compassionate use’

Summary The 2024 Nipah outbreak in Kerala, India —its fifth in six years—and the recurring annual outbreaks in Bangladesh underscore the persistent threat posed by the Nipah virus (NiV) in the region. With a high mortality rate, human-to-human transmission potential , and the widespread presence of Pteropus bats , the natural reservoir, NiV remains a significant epidemic threat . Despite being a WHO priority pathogen , there has been no systematic effort to improve patient care for NiVD, leading to consistently poor outcomes . Current care relies on supportive measures and the ‘ compassionate use ’ of unapproved drugs like ribavirin and remdesivir . Drugs used ‘off-label’ during outbreaks can become the ‘standard of care’ without robust evidence of their safety or efficacy, complicating the testing of new therapies and perpetuating uncertainty about their true effectiveness. To improve NiVD care, we propose four key strategies: 1) Enhance early case detection , 2) optimize supportive c...

New incursions of #H5N1 clade 2.3.4.4b highly pathogenic avian #influenza viruses in wild #birds, South #Korea, October 2024

{Excerpt} Highly pathogenic avian influenza (HPAI) subtype H5Nx viruses of the A/Goose/Guangdong/1/1996 (Gs/Gd) lineage have led to substantial economic losses within the poultry industry and represent an ongoing public health threat (1). The Gs/Gd lineage H5 viruses not only have evolved into 10 primary clades 0–9 with their subclades but are also reassorted with other influenza A viruses (2–4). Notably, since 2020, clade 2.3.4.4b HPAI H5N1 viruses have caused outbreaks across a broad geographic range, including Asia, Europe, Africa, North America, South America, and Antarctica (5–7). The infections of HPAI H5N1 viruses in mammals including wild, domestic, and humans underscore the potential zoonotic risk and pandemic potential of these evolving H5 viruses (8). (...) Source: Frontiers in Veterinary Sciences,  https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2024.1526118/full ____

#USA - High pathogenicity avian #influenza #H5N9 viruses (#poultry) (Inf. with) - Immediate notification

Highly pathogenic avian influenza (HPAI) H5N9, Eurasian lineage goose/Guangdong clade 2.3.4.4b and HPAI H5N1 clade 2.3.4.4b were confirmed in a commercial duck premises in Merced County, CA . This is the first confirmed case of HPAI H5N9 in poultry in the United States. The USDA Animal and Plant Health Inspection Service (APHIS), in conjunction with State Animal Health and Wildlife Officials, are conducting comprehensive epidemiological investigations and enhanced surveillance in response to the HPAI related events. Source: WOAH,  https://wahis.woah.org/#/in-review/6201 _____

#Bussuquara Virus: A Neglected #Orthoflavivirus with Broad Distribution Across Central and South #America and the #Caribbean

Abstract Bussuquara virus (BSQV) was first discovered in the Brazilian Amazon in 1956 . It is an arthropod-borne virus (arbovirus) in the genus Orthoflavivirus , family Flaviviridae . Since its discovery, BSQV has been sporadically detected across the South ( Brazil, Columbia, and Argentina ) and Central ( Panama and Mexico ) America and the Caribbean ( Grenada ), but there is minimal BSQV surveillance due to limited public health awareness and a lack of specific or sensitive diagnostics. BSQV exposure has been reported in a wide range of host and vector species , including humans . Little information is available in the literature and herein we summarize the published historical findings on BSQV and suggest a pathway for future studies to better understand its potential emergence into human populations. Source: Viruses,  https://www.mdpi.com/1999-4915/17/2/183 _____

Estimating the #generation time for #influenza #transmission using #household data in the #USA

Abstract The generation time , representing the interval between infections in primary and secondary cases , is essential for understanding and predicting the transmission dynamics of seasonal influenza , including the real-time effective reproduction number (Rt). However, comprehensive generation time estimates for seasonal influenza, especially since the 2009 influenza pandemic, are lacking. We estimated the generation time utilizing data from a 7-site case-ascertained household study in the United States over two influenza seasons, 2021/2022 and 2022/2023. More than 200 individuals who tested positive for influenza and their household contacts were enrolled within 7 days of the first illness in the household. All participants were prospectively followed for 10 days, completing daily symptom diaries and collecting nasal swabs, which were then tested for influenza via RT-PCR. We analyzed these data by modifying a previously published Bayesian data augmentation approach that imputes in...

The first reported case of #candidemia caused by the novel #Candida tropicalis diploid sequence type 1515

Abstract Introduction :  Since the dawn of the new millennium, Candida species have been increasingly implicated as a cause of both healthcare-associated as well as opportunistic yeast infections , due to the widespread use of indwelling medical devices , total parenteral nutrition , systemic corticosteroids , cytotoxic chemotherapy , and broad-spectrum antibiotics. Candida tropicalis is a pathogenic Candida species associated with considerable morbidity, mortality , and drug resistance issues on a global scale. Methodology :  We report a case of a 43-year-old man who was admitted to our hospital for further management of severe coronavirus disease 2019 (COVID-19) pneumonia . During his stay in the ward, he received systemic corticosteroids for a total duration of 32 days. A broad-spectrum antibiotic (piperacillin-tazobactam) was also given due to copious amounts of tracheostomy secretions . Results :  The patient’s fever recurred following an afebrile interval of 11 days...

Fire-Swept Hills, Tom Thomson (1915)

  Public Domain. Source: WikiArt,  https://www.wikiart.org/en/tom-thomson/fire-swept-hills-1915 _____

#Hemagglutinin with a #polybasic #cleavage site confers high #virulence on #H7N9 avian #influenza viruses

Abstract H7N9 avian influenza virus (AIV) first emerged in February 2013 in China , and early isolates were all low pathogenic (LP). After circulation for a few years in live poultry markets of China , LP H7N9 AIVs evolved into a highly pathogenic (HP) form in late 2016. Deduced amino acid sequence analysis of hemagglutinin (HA) gene revealed that all HP H7N9 AIVs have obtained four-amino-acid insertion at position 339-342 (H7 numbering), making the cleavage site from a monobasic motif (LP AIVs) to a polybasic form (HP AIVs). Notably, the polybasic cleavage site motifs are diversified, of which PEVPKRKRTAR↓GLF motif is prevalent. To elucidate the reasons accounting for its dominance, recombinant H7N9 virus carrying PEVPKRKRTAR↓GLF (rJT157-2) motif was generated based on LP H7N9 virus A/chicken/Eastern China/JT157/2016 (JT157). Besides, another two viruses containing PEVPKGKRTAR↓GLF (rJT157-1) and PEIPKRKRTAR↓GLF (rJT157-3) cleavage site motifs were also constructed as comparisons. We f...

#Coronavirus Disease Research #References (by AMEDEO, January 25 '25)

  Antiviral Res XU M, Zhang Z, Sun Y, Mai H, et al IgA class switching enhances neutralizing potency against SARS-CoV-2 by increased antibody hinge flexibility. Antiviral Res. 2025 Jan 17:106082. doi: 10.1016/j.antiviral.2025.106082. PubMed           Abstract available CHUTIWITOONCHAI N, Akkarawongsapat R, Chantawarin S, Jiarpinitnun C, et al Antiviral effect of pinostrobin, a bioactive constituent of Boesenbergia rotunda, against porcine epidemic diarrhea virus. Antiviral Res. 2025;234:106073. PubMed           Abstract available BMJ AGIUS RM Healthcare workers should get covid-19 vaccinations. BMJ. 2025;388:r89. PubMed          Graefes Arch Clin Exp Ophthalmol KIM W, Park CM, Choi YJ, Kim DH, et al Recent trends and outcomes in immediate and delayed sequential bilateral cataract surgeries: a nationwide cohort study in South Korea. Graefes Arch Clin Exp ...

#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, Jan. 25 '25)

  Ann Intern Med VALE CL, Godolphin PJ, Fisher DJ, Higgins JPT, et al Anticoagulation Among Patients Hospitalized for COVID-19 : A Systematic Review and Prospective Meta-analysis. Ann Intern Med. 2024 Dec 24. doi: 10.7326/ANNALS-24-00800. PubMed           Abstract available Antiviral Res GAO M, Zhang Z, Yao G, Zhang L, et al Design, synthesis, and biological evaluation of novel 2'-deoxy-2'-spirooxetane-7-deazapurine nucleoside analogs as anti-SARS-CoV-2 agents. Antiviral Res. 2024 Dec 30:106060. doi: 10.1016/j.antiviral.2024.106060. PubMed           Abstract available MERCURI FA, Anderson GP, Miller BE, Demaison C, et al Discovery and development of INNA-051, a TLR2/6 agonist for the prevention of complications resulting from viral respiratory infections. Antiviral Res. 2024 Dec 27:106063. doi: 10.1016/j.antiviral.2024.106063. PubMed           Abstr...

#Remdesivir and #Obeldesivir Retain Potent #Antiviral Activity Against #SARS-CoV-2 #Omicron Variants

Abstract As new SARS-CoV-2 variants continue to emerge , it is important to evaluate the potency of antiviral drugs to support their continued use. Remdesivir (RDV; VEKLURY®) an approved antiviral treatment for COVID-19, and obeldesivir (ODV) are inhibitors of the SARS-CoV-2 RNA-dependent RNA polymerase Nsp12. Here we show these two compounds retain antiviral activity against the Omicron variants BA.2.86, BF.7, BQ.1, CH.1.1, EG.1.2, EG.5.1, EG.5.1.4, FL.22, HK.3, HV.1, JN.1, JN.1.7, JN.1.18, KP.2, KP.3, LB.1, XBB.1.5, XBB.1.5.72, XBB.1.16, XBB.2.3.2, XBC.1.6, and XBF when compared with reference strains. Genomic analysis identified 29 Nsp12 polymorphisms in these and previous Omicron variants. Phenotypic analysis of these polymorphisms confirmed no impact on the antiviral activity of RDV or ODV and suggests Omicron variants containing these Nsp12 polymorphisms remain susceptible to both compounds. These data support the continued use of RDV in the context of circulating SARS-CoV-2 vari...

#Detection of low pre-existing #humoral #immunity against #influenza virus #H5N1 clade 2.3.4.4b in unexposed individuals

Abstract The repeated spill-over of Influenza A virus H5N1 clade 2.3.4.4b from cattle to humans highlights the risk of a human H5N1 pandemic . Given the impact of pre-existing immunity on the course and severity of viral infections , we assessed in detail the humoral immunity against the H5N1 A/Texas/37/2024 isolate in H5N1-naive individuals . To this end, we performed complementary binding and neutralization assays on 66 subjects and ranked activities among a panel of 76 influenza A virus isolates . We detected low but distinct cross-neutralizing titers against A/Texas/37/2024 with a 3.9 to 15.6-fold reduction compared to selected H1N1 or H3N2 strains. Moreover, by cloning and evaluating 136 monoclonal antibodies from single memory B cells , we identified potent A/Texas/37/2024-neutralizing monoclonal antibodies in five out of six investigated individuals. These antibodies predominantly utilize VH1-69 gene segments, cross-neutralize H1, and compete with antibodies targeting the HA ste...

Novel introductions of #human-origin #H3N2 #influenza viruses in #swine, #Chile

Abstract Influenza A virus (IAV) continuously threatens animal and public health globally , with swine serving as a crucial reservoir for viral reassortment and evolution . In Chile , H1N2 and H3N2 subtypes were introduced in the swine population before the H1N1 2009 pandemic, and the H1N1 was introduced from the H1N1pdm09 by successive reverse zoonotic events . Here, we report two novel introductions of IAV H3N2 human-origin in Chilean swine during 2023. Our study reveals a closer relationship between recent human seasonal H3N2 and novel swine strains. Interestingly, one strain maintains all the genes from the original human virus , but the other strain is already a reassortment of human H3N2 and an H1N2 previously observed on the farm. Observing global IAV sequences, a similar pattern was identified in the USA confirming the reverse zoonotic potential of current seasonal human H3N2 strains. These results highlight the importance of ongoing surveillance and reinforcing biosecurity in ...

Phylogeography and biological characterization of #H12N2 virus isolated from whooper #swan in Central #China

Abstract Wild birds and waterfowl serve as the natural reservoirs of avian influenza viruses (AIVs). When AIVs originating from wild birds cross species barriers to infect mammals or humans , they pose a significant threat to public health . The H12 subtype of AIVs primarily circulates in wild birds, with relatively few isolates reported worldwide , and the evolutionary and biological characteristics of H12 subtype AIVs remain largely unknown. In this study, we analyzed the spatiotemporal distribution of H12 subtype AIVs worldwide and conducted a comprehensive investigation into the evolutionary and biological characteristics of an H12N2 virus isolated from a whooper swan in Central China . Phylogenetic analysis revealed that the H12N2 isolate belongs to the Eurasian lineage , with its HA gene likely originating from a duck-derived H12N5 virus and its NA gene potentially derived from an H9N2 virus , indicating that it is a complex reassorted virus. Animal experiments in domestic ducks ...