ETIDIOH - NEW

  ABSTRACT The ease with which emerging SARS-CoV-2 variants escape neutralizing antibodies limits the protection afforded by a prior exposure , be it infection or vaccination. While rare, broadly neutralizing antibodies with activity toward diverse sarbecoviruses have been detected in convalescent serum . Motivated by findings that plasma responses show increased neutralization breadth and potency with continued antigen exposure , we isolated monoclonal antibodies (mAbs) after a SARS-CoV-2 re-infection and compared them to those isolated 1 year prior, after the first breakthrough infection. Among clonal lineage members identified at both time points, mAbs from the later time point showed improved neutralization potency and breadth . One mAb isolated after re-infection, C68.490, targets a conserved region in the receptor binding domain and shows remarkable activity not only against SARS-CoV-2 variants, but also diverse sarbecoviruses from more distant clades present in animal reserv...

  Abstract As part of its role in the World Health Organization (WHO) Global Influenza Surveillance and Response System (GISRS), the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne received 12,180 human influenza-positive samples during 2024 . Viruses were analysed for their antigenic, genetic, and antiviral susceptibility properties . Selected viruses were propagated in qualified cells or embryonated hens’ eggs for potential use in seasonal influenza virus vaccines. During 2024 , influenza A( H1N1 )pdm09 and A( H3N2 ) viruses predominated , accounting for 33% and 42%, respectively, of all viruses received, compared to 5% for influenza B/Victoria . Of note, one influenza A(H5N1) virus was also received in 2024 . The majority of A(H1N1)pdm09 (98%), A(H3N2) (88%) and influenza B (100%) viruses analysed at the Centre were found to be antigenically and genetically similar to the respective WHO recommended vaccine strains for the Southern Hemisphere in 2024...

  Abstract Newly emerging influenza virus strains pose a constant threat as they encounter a population lacking neutralizing antibodies against the new strain . However, cross-reactive non-neutralizing antibodies (nnABs) may be present and assist in mitigating disease symptoms via various effector mechanisms, including antibody-dependent cellular cytotoxicity (ADCC). Although nnABs to influenza virus have received more attention lately , little information is available on their age-related prevalence , steady-state levels, functional properties , and changes in these parameters over time. Using longitudinal samples from adolescents, adults, and older adults , collected before and after the 2009 swine flu pandemic , we comprehensively characterized the specificity and functionality of nnAB responses against H1N1 pandemic 2009 (H1N1pdm09) virus . Remarkably, all participants exhibited cross-reactive antibodies to this virus before having encountered it through infection or vaccinatio...

  Abstract Background :  Genetic drift and host-associated adaptation in influenza A viruses threaten the long-term reliability of RT-qPCR-based diagnostics , particularly when nucleotide mismatches arise within primer and probe binding regions . Conventional assay evaluations often emphasize sequence conservation but rarely assess functional mismatch tolerance across divergent subtypes and hosts.  Methods :  We performed an in silico evaluation of a matrix (M) gene–targeted RT-qPCR assay by aligning primer and probe binding regions against 22 H1N1 isolates and representative H3N2 and H5N1 reference strains, including recent zoonotic isolates from avian and bovine hosts . Nucleotide mismatches were identified, quantified, and mapped relative to assay components and oligonucleotide termini. Mismatch burden was summarized by subtype and assay region.  Results :  H1N1 isolates exhibited complete conservation across primer and probe regions. In contrast, H3N2 a...

  ABSTRACT The recent emergence of highly pathogenic avian influenza (HPAI) H5N1 (clade 2.3.4.4b, genotype B3.13) in dairy cattle presents substantial challenges to the agricultural sector and public health. Mechanistic studies of infection and transmission in cattle have proven difficult due to animal handling restrictions and the limited availability of established cell culture models. Primary bovine embryonic fibroblasts (BeEFs) were isolated and investigated here as a model to study influenza A virus (IAV) infection dynamics. We compared sialylation profiles , infectious virus production, viral replication, and plaque morphology in BeEFs following infection with the bovine HPAI H5N1 and an earlier 2.3.4.4b genotype (B1.1) isolated in 2022. The data presented here demonstrate increased expression of α-2,3 sialic acids compared to α-2,6 sialic acids in BeEFs , similar to sialylation profiles previously reported in bovine mammary tissue . These data also display increased viral fi...

  Abstract Molnupiravir induces mutations that render severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication-competent through error catastrophe mechanisms . Previous studies showed no resistant virus emergence during prolonged molnupiravir treatment, with no resistant variants reported . However, these approaches were limited by genetic uniformity at passage initiation. To investigate viral population dynamics under enhanced genetic diversity, we employed mutagenic pre-treatment using 5-fluorouracil (5-FU) and favipiravir to generate diverse quasi-species populations before molnupiravir selection pressure. Viral populations were treated with stepwise increasing molnupiravir concentrations (10 μM ⟶ 25 μM ⟶ 40 μM) over ten serial passages . Viral detectability, plaque morphology, and mutation accumulation were analyzed using molecular and sequencing approaches . Only high-concentration favipiravir (1000 μM) pre-treatment maintained detectable viral RNA through ten ...

  Abstract The recent emergence of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b in U.S. dairy cattle marks a pivotal shift in the ecology of influenza A viruses (IAVs), signaling an unexpected expansion into a major livestock species . This review explores the molecular mechanisms underpinning this cross-species transmission , focusing on the unique sialic acid receptor landscape of the bovine mammary gland as a critical determinant. We synthesize emerging evidence that this tissue, which co-expresses both avian-type (α2,3-linked) and human-type (α2,6-linked) sialic acid receptors , functions as a novel biological crucible for viral adaptation . Within this environment, H5N1 virus faces selective pressure for hemagglutinin (HA) mutations —such as Q226L and N193D—that can alter receptor binding specificity toward human-like glycans , potentially bridging the species barrier. Recent studies confirm that bovine H5N1 virus isolates exhibit dual receptor-binding avidity ...

  Abstract The spillover of highly pathogenic avian influenza (HPAI) A H5N1 virus to mammalian hosts raises major concerns due to its pandemic potential . Cats are frequently affected mammals, often succumbing to systemic and neurological disease . Here, we characterized the pathogenesis and transmissibility of two H5N1 genotypes, B3.13 and D1.1, in cats . Infected cats exhibited high-level viremia and virus shedding in nasal, oral, and fecal secretions were consistently detected. The virus replicated initially in the upper respiratory tract and lungs , followed by systemic dissemination and neuroinvasion . Notably, the virus crossed the blood-brain-barrier by infecting endothelial cells , spreading to astrocytes and neurons , causing multifocal encephalitis . D1.1-virus infection caused protracted disease with lower shedding and no transmissibility , whereas B3.13 virus caused rapid onset with efficient shedding and transmission. These findings reveal critical H5N1 neuropathogenes...

  Antiviral Res LIU Q, Tang B, Xuan X, Wang H, et al The potential of leritrelvir repositioning for the treatment of coxsackievirus B4 and common enterovirus infections. Antiviral Res. 2026 Feb 16:106367. doi: 10.1016/j.antiviral.2026.106367. PubMed           Abstract available Emerg Infect Dis KASAI M, Sakuma H, Suzuki M, Nishiyama M, et al Life-Threatening SARS-CoV-2-Associated Encephalopathy and Multiorgan Failure in Children, Asia and Oceania, 2022-2024. Emerg Infect Dis. 2026;32:169-179. PubMed           Abstract available Int J Infect Dis MA Q, Yao L, Ding H, Tian W, et al SARS-CoV-2 Variant Specific Protective Immunity and Long-term Immune Recovery in People Living With HIV: A Retrospective Cohort Study. Int J Infect Dis. 2026 Feb 16:108491. doi: 10.1016/j.ijid.2026.108491. PubMed           Abstract available J Med Virol EXPRESSION OF CONCERN: Resistance-As...

  Antiviral Res WRONSKI S, Obernolte H, Schaudien D, Braun A, et al Prophylactic intranasal administration of bacterial lysate OM-85 mitigates human rhinovirus (RV-A1b) lung infection and inflammation in mice. Antiviral Res. 2026;247:106362. PubMed           Abstract available HEDSKOG C, Rodriguez L, Hu Y, Li J, et al SARS-CoV-2 Resistance Analyses From the Phase 3 BIRCH Study of Obeldesivir in High-Risk Nonhospitalized Participants With COVID-19. Antiviral Res. 2026 Jan 19:106351. doi: 10.1016/j.antiviral.2026.106351. PubMed           Abstract available RODRIGUEZ L, Hu Y, Li J, Han D, et al SARS-CoV-2 Resistance Analyses From the Phase 3 OAKTREE Study of Obeldesivir in Low-Risk Nonhospitalized Participants With COVID-19. Antiviral Res. 2025 Dec 29:106339. doi: 10.1016/j.antiviral.2025.106339. PubMed           Abstract available Arch Virol LIM KS, Selvan ME, Ea CK...

  ABSTRACT Dogs are considered mixing vessels for influenza viruses , posing a pandemic potential via viral reassortment . Our previous studies indicated that the avian-origin H3N2 canine influenza virus (A/canine/Zhejiang/1/2010, abbreviated C1) is virulent in canine and mice . Furthermore, we found that the HA and NA genes of C1 share a close genetic relationship with an H3N2 avian influenza virus (A/duck/Shanghai/06/2009, abbreviated D6), but they exhibit distinct pathogenicity . However, the understanding mechanisms remain unclear. In the present study, we explored the genetic determinants that contribute to the different pathogenicity between the C1 and D6. By using the reverse genetics approaches, we rescued several single-gene and position-substituted reassortant viruses based on the C1. The replication in Madin–Darby canine kidney cells and pathogenic trial in mice showed that the neuraminidase (NA) gene played a critical role in C1 virulence. Further analysis demonstrated ...

  Abstract Intercontinental spread of highly pathogenic avian influenza A(H5N1) viruses poses significant pandemic risks and necessitates strong protective countermeasures . We evaluated the therapeutic efficacy of the neuraminidase inhibitor oseltamivir , the polymerase inhibitors baloxavir and favipiravir , and an ion-channel blocker amantadine , against severe influenza A( H5N1 ) virus infection in female BALB/c mice . Baloxavir (≥10 mg/kg, 1 dose) fully protected mice from death , significantly reduced virus respiratory replication, and prevented neuroinvasion . Oseltamivir (≥100 mg/kg/day for 5 days) provided limited survival benefits , reduced lung titers but failed to prevent viral neuroinvasion . Favipiravir (≥100 mg/kg/day for 5 days) provided partial protection , although did not reduce viral titers in lungs and brain . Amantadine provided no benefits . Although all drugs inhibited A(H5N1) viruses in vitro, in vivo correlations did not extend beyond baloxavir . Our result...

  Highlights •  Global Health Impact : Improved influenza vaccines have the potential to avert between 6.6 and 18 billion additional influenza cases, prevent 2.3 to 6.2 million additional deaths, and save 21 to 57 million disability-adjusted life years (DALYs) globally beyond those averted by current seasonal influenza vaccines •  Cost-Effectiveness : Depending on the price, coverage, and vaccine characteristics, improved influenza vaccines could be cost-effective in 9 to 48 % of countries, offering substantial global economic value under most scenarios •  Financial Viability : The development and commercialization of improved influenza vaccines present a robust financial value proposition, with positive net present value (NPV) across all vaccine profiles •  Policy and Decision Making : Vaccine efficacy, duration of protection, and breadth of protection are key factors influencing the adoption of improved influenza vaccines in national immunization programs •...

  ABSTRACT Swine influenza A virus (swIAV) is an important pathogen with regard to both the swine industry and public health . The pandemic A(H1N1) 2009 outbreak was caused by the swine-origin pandemic A(H1N1) 2009 [A(H1N1)pdm09] virus. Several reports have shown that several amino acid substitutions in the hemagglutinin (HA) antigenic sites can alter HA antigenicity. However, the impact of the amino acid deletion at position 155 on HA antigenicity remains unknown. In this study, we have isolated 11 samples of swIAVs from seven pig farms in Japan and found an amino acid deletion at position 155 of the HA region in one of the isolates of the H1N2 subtype . To examine the impact of this amino acid deletion on viral replication and HA antigenicity, we generated recombinant influenza A viruses possessing the H1 HA gene encoding either an artificial insertion or deletion of glycine at position 155. The growth kinetics of these recombinant viruses in two different cell lines demonstrated...

  Abstract Objective The H7N9 avian influenza virus, identified in China in 2013, has posed a significant threat to public health due to its high mortality rate . This systematic review aims to evaluate the clinical characteristics and mortality risk factors of H7N9 patients. Methods English and Chinese databases (PubMed, Web of Science, Embase, CNKI, VIP, Wanfang) were searched for studies on laboratory-confirmed H7N9 cases with available data on symptom onset, diagnosis time, clinical features, oseltamivir administration, and outcomes . Univariate and multivariate analyses were performed on the pooled case data to assess the relationship between clinical factors and mortality risk. Results A total of 166 studies including 237 H7N9 cases were analyzed , with an overall mortality rate of 41.77%. Univariate analysis showed higher mortality in patients with advanced age ≥ 66 years (62.50%), those with underlying diseases (60.20%), those who received oseltamivir ≥ 8 days after symptom...

  Abstract B etween 2022 and 2025, highly pathogenic avian influenza viruses (HPAIVs) of clade 2.3.4.4b, including four distinct H5 Eurasian (EA) genotypes , were detected in wild birds and mammals in the Svalbard Archipelago and on the island of Jan Mayen . We describe their epidemiology and genomic characteristics to improve understanding of HPAIV occurrence and transmission in the High Arctic . The initial cases in 2022 occurred during summer and involved a glaucous gull (Larus hyperboreus) and great skuas (Stercorarius skua) on Svalbard and Jan Mayen , representing the first detections of HPAIVs in the High Arctic . Three HPAIV genotypes were identified: EA-2020-C (H5N1), EA-2021-AB (H5N1), and EA-2021-I ( H5N5 ). In 2023 , HPAIVs were detected in a broader range of bird species, and retrospectively in an Atlantic walrus reported by another research group (Odobenus rosmarus rosmarus). Genotypes identified in 2023 were EA-2020-C (H5N1), EA-2021-I ( H5N5 ), and EA-2022-BB (H5N1)....

  Highlights •  Concern over H5N1 bird flu testing and detection in the Netherlands is increasing. •  50 human laboratories in the Netherlands, Aruba, Bonaire , and Curacao were assessed. •  The laboratories detected animal influenza viruses with high performance. •  Few laboratories identified the animal subtype of detected influenza A viruses. •  National reference laboratory capacity to identify the animal subtype is critical. Abstract Background Since 2022, highly pathogenic H5N1 influenza A virus clade 2.3.4.4b has caused global outbreaks among wild birds and poultry , with increasing mammalian and sporadic human infections . This elevates concerns about zoonotic transmission and pandemic risk , highlighting the need for accurate detection and identification of animal influenza A viruses by human clinical diagnostic laboratories (hCDL). Methods To evaluate routine diagnostic performance , an External Quality Assessment (EQA) panel containing inactivate...

  Abstract Despite Antarcticas geographic isolation, the first incursion of high pathogenicity avian influenza (HPAI) H5N1 was detected in the 2023/24 austral summer . Surveillance for HPAI H5N1 in Antarctica remains patchy due to logistical, financial, and infrastructure challenges , with many suspected cases remaining unconfirmed , and few viral genomes sequences available to date. Through the 2024/25 austral summer we undertook five sampling expeditions to the South Shetland Islands and Antarctic Peninsula facilitated by cruise ships/operators. Across more than 500 faecal environmental samples collected from apparently healthy penguins and marine mammals , we found no detectable evidence of HPAI H5N1 . However, HPAI H5N1 was detected in all but one of the skua carcasses sampled , which, in most cases, were found within meters of penguin sub-colonies . All HPAI H5N1 viral genomes sequences from skuas on the Antarctic Peninsula fell within a single lineage, which included those ge...