ETIDIOH - NEW

  September 2025   The development of influenza candidate vaccine viruses (CVVs), coordinated by WHO, remains an essential component of the overall global strategy for influenza pandemic preparedness . Selection and development of CVVs are the first steps towards timely vaccine production and do not imply a recommendation for initiating manufacture . National authorities may consider the use of one or more of these CVVs for pilot lot vaccine production , clinical trials and other pandemic preparedness purposes based on their assessment of public health risk and need.  Zoonotic influenza viruses continue to be identified and evolve both antigenically and genetically, leading to the need for additional CVVs for pandemic preparedness purposes.  Changes in the antigenic and genetic characteristics of these viruses relative to existing CVVs and their potential risks to public health justify the need to develop new CVVs. This document summarizes the antigenic and genetic c...

  New human cases {1,2}:  -- From 26 August to 29 September 2025 , based on reporting date, the detection of influenza A(H5) in one human , influenza A(H5N1) in one human , influenza A(H9N2) in eight humans and an influenza A(H1N1) variant ((H1N1)v) virus in one human were reported officially.   Circulation of influenza viruses with zoonotic potential in animals :  -- High pathogenicity avian influenza (HPAI) events in poultry and non-poultry animal species 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}:  -- Sustained human to human transmission has not been reported from these events.  -- Based on information available at the time of this risk assessment update , the overall public health risk from currently known influenza A viruses d...

  Abstract The antigenic relationship between Eurasian avian-like H1N1 swine influenza viruses (EA H1N1) and human pandemic 2009 H1N1 viruses (2009/H1N1) remains a critical question for influenza surveillance and vaccine efficacy . This study systematically investigated the antigenic differences between strains A/swine/Tianjin/312/2016 (TJ312, EA H1N1) and A/Guangdong-Maonan/SWL1536/2019 (GD1536, 2009/H1N1). Cross-hemagglutination inhibition (HI) assays revealed a significant antigenic disparity, with a 16-fold reduction in heterologous versus homologous HI titers . Comparative sequence analysis identified 22 amino acid differences across the five major antigenic sites (Sa, Sb, Ca1, Ca2, and Cb) of the HA1 subunit. Using reverse genetics , a panel of mutant viruses was generated. This study revealed that a single histidine (H)-to-asparagine (N) substitution at residue 128 (H3 numbering) in the Sa antigenic site acts as a primary determinant of antigenic variation , sufficient to ca...

  ABSTRACT Swine influenza A virus (swIAV) is an important zoonotic pathogen with the potential to cause human influenza pandemics . Swine are considered “ mixing vessels ” for generating novel reassortant influenza A viruses . In 2009, a swine-origin reassortant virus (2009 pandemic H1N1, pdm/09 H1N1 ) spilled over to humans , causing a global influenza pandemic . This virus soon spread back into swine herds and reassorted with the circulating swIAVs. We previously reported that the genotype 4 (G4) reassortant Eurasian avian-like (EA) H1N1 virus , which bore pdm/09- and triple reassortant (TR)-derived internal genes, had been predominant in swine populations of China since 2016, posing a threat to both the swine industry and public health . Here, our ongoing surveillance confirmed that G4 EA H1N1 viruses remained the predominant swIAVs in China from 2019 to 2023 and had reassorted with the co-circulating swIAVs, such as the H3N2 virus, to generate novel reassortant EA H1N2 viruses...

  Abstract In recent years, the four main swine influenza A virus (IAV-S) subtypes circulating in swine in the EU have been H1avN1, H1huN2, H1N1pdm09, and H3N2 . The latter emerged in 1984 from a reassortment event between a human seasonal H3N2 and H1avN1, and is currently detected at low prevalence in swine in Italy . Here, we describe nine H3N2 IAV-S isolates belonging to three novel genotypes , first detected in Italy in 2021 , likely resulting from reassortment events between swine and human IAVs. The first genotype was characterized by a hemagglutinin (H3 HA) of human seasonal origin , a neuraminidase (N2 NA) derived from H1huN2 strains circulating in Italian swine, and an avian-like internal gene cassette (IGC). The second genotype differed in its IGC constellation: PB2, PB1, PA and NP segments were of pandemic origin ( pdm09 ), while NS and M segments derived from the Eurasian avian-like lineage . The third genotype combined a human-derived H3, a Gent/84-derived N2, and a pd...

  ABSTRACT Influenza A virus (IAV) in swine in the U.S. is surveilled to monitor genetic evolution to inform intervention efforts and aid pandemic preparedness . We describe data from the U.S. Department of Agriculture National Surveillance Plan for Influenza A Virus in Pigs from 2009 to 2022. Clinical respiratory cases were subtyped, followed by sequencing of hemagglutinin (HA) and neuraminidase (NA), and a subset of viruses was whole genome sequenced . Phylogenetic analysis identified geographic and temporal IAV reassortment hotspots . Regions acting as IAV genomic diversity sources or sinks were quantified, and dissemination was qualified and modeled. The dominant IAV clades were H1N2 (1B.2.1), H3N2 (1990.4.a), and H1N1 (H1-1A.3.3.3-c3). Internal genes were classified as triple-reassortant (T) or pandemic 2009 (P), and three genome constellations represented 73.5% of detections across the last 2 years. In some years, the distribution of IAV diversity was so narrow that it presen...

Abstract The H1N1 swine influenza viruses CQ91 and CQ445, isolated from pigs in China, exhibited distinct virulence in mice despite sharing similar genomic constellations. CQ91 demonstrated higher pathogenicity (MLD50: 5.4 log10 EID50) and replication efficiency in mice compared to CQ445 (MLD50: 6.6 log10 EID50). Through reverse genetics, we found that the attenuation of CQ445 was due to a single substitution of glutamic acid (E) with lysine (K) at position 343 in the PB2 protein . Introducing the CQ445-PB2 (343K) into CQ91 significantly reduced viral replication and pathogenicity in mice, while replacing CQ445-PB2 with CQ91-PB2 (343E) restored virulence. In vitro studies showed that the K343E mutation impaired viral replication in MDCK and A549 cells and reduced polymerase activity in minigenome assays. Mechanistically, the amino acid at position 343 in the PB2 affects the transcription stage of the viral replication process . Structural modeling indicated that the charge reversal cau...

ABSTRACT Newly emerging or “re-emerging” influenza viruses have been regarded as a huge global threat to human public health . However, there are few reports of human deaths caused by newly emerging influenza viruses derived from pigs and poultry . Here, we described the clinical and virological features of a fatal encephalitis caused by a novel H3N2 reassortant virus generated from swine H3N2 and human H7N9 viruses. A 7-year-old boy was diagnosed with acute encephalitis in Yixing, China, in August 2022. Chest computed tomography (CT) showed mild pneumonia . Brain CT indicated acute encephalitis companied brain parenchyma swelling. Haematological examinations revealed a markedly elevation of lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, creatine kinase and cytokines . Pathogenic analysis confirmed that a novel H3N2 virus (A/Yixing/805/2022, YX805) was responsible for this case. Phylogenetic analysis showed that the surface protein-coding genes were origin...

ABSTRACT H1 and H3 influenza A viruses (IAVs) circulating in European pigs are markedly distinct from those circulating in other global swine populations . These viruses exhibit significant genetic diversity , further expanded by periodic interspecies transmission of IAVs from humans into pigs , followed by sustained circulation. Several zoonotic IAV infections in humans in Europe have been associated with the 1C lineage of H1 IAVs . Given the predominance of H1 detections in pigs and their zoonotic potential, we quantified antigenic evolution of H1 viruses in European pigs using ferret and pig models and assessed diversity relative to swine IAV vaccine strains. Ferret and swine antisera comparisons revealed no significant differences in antibody responses . Viruses of the 1A.3.3.2 clade exhibited reduced cross-reactivity to human seasonal vaccine strains from 2009. Viruses of the 1B.1.2.2 clade showed no cross-reactivity to the 1978 human seasonal influenza viruses nor to candidate va...

Abstract The Eurasian avian-like swine (EA) H1N1 virus has been widely prevalent in the Chinese swine population and has caused infections in human . However, knowledge regarding its pathogenic mechanisms remains limited. In this study, we analyzed the pathogenic determinants of two G4 genotype EA H1N1 viruses (A/Swine/Guangdong/SS12/2017 and A/Swine/Jiangxi/1110/2017) with differing pathogenicity by constructing a series of reassortant and mutant viruses . The HA-G219A mutation was found to be determinant of pathogenicity in mice. Subsequent analyses revealed that this mutation enhances viral replication in human cells , improves thermal stability , reduces HA activation pH, and alters receptor-binding properties . Furthermore, HA-G219A mutation may be an adaptive mutation that facilitates influenza virus adaptation to swine , with its prevalence increasing in the swine population. This mutation may support cross-species transmission of EA H1N1 swine influenza viruses or genetic excha...

Abstract Swine Influenza A Virus (IAV-S) poses a significant burden to both the pork industry and public health . Current vaccines against IAV-S are infrequently updated and induce strain-specific immunity. Computational platforms have recently emerged as a promising strategy to develop new-age vaccines. Here, we describe the Epigraph , a computationally derived and epitope optimized set of vaccine immunogens. When compared to wildtype immunogens (WT) and a commercial comparator (FluSure XP®), pigs immunized with Epigraph demonstrate significantly improved breadth and magnitude of antibody responses . Further, pigs immunized with Epigraph show more robust and a wider breadth of cross-reactive cell-mediated immune responses than pigs immunized with WT immunogens. In an experimental infection model , Epigraph immunized pigs demonstrate a significant reduction of clinical disease, lower shedding of infectious virus, reduction of lung lesions, and lower microscopic immunopathology compared...

Abstract Surveillance of influenza A viruses in pigs (SwIAV) is critical for identification of novel genetic groups that pose a risk to pig health and might have zoonotic potential . SwIAVs circulating in pigs in England between 2014 and 2021 were characterised using whole genome sequencing (WGS). Haemagglutinin (HA) and neuraminidase (NA) sequencing data from 82 of 368 influenza A positive samples (71 submissions) were determined, identifying H1N1 and H1N2 subtypes from the 1A classical swine and 1B human-seasonal lineages respectively. The 1B lineage viruses were predominant, accounting for 68.29% of sequenced viruses, with 1A lineage viruses comprising 31.71%, primarily from the 1A.3.3.2 clade (2009 H1N1 pandemic origin). This study characterised previously undefined diversity within the 1B lineage which led to the designation of new HA clades 1B.1.1.1, 1B.1.1.2 and 1B.1.1.3. Complete genome data were obtained from 64/82 viruses thereby updating the definition of genetic diversity t...

Abstract Background and Objectives :  The Netherlands faces zoonotic disease risks due to its dense human and livestock populations . The 2009 H1N1 outbreak highlighted the pandemic potential of influenza virus reassortment. Effective preparedness requires integrating behavioural and epidemiological models . Human behaviour, shaped by personal, social, and institutional factors , is critical in detecting, intervening, and treating diseases. Using the Theory of Planned Behaviour (TPB), a framework was developed integrating knowledge from the TPB to improve early detection and response, using (zoonotic) swine influenza as a case study.  Material and Methods :  Within the framework we defined the desired outcome : timely detection and notification of symptomatic (and hypothetical zoonotic) swine influenza to prevent its spread. Actions, such as symptom recognition and disease reporting, were linked to key drivers extracted from the TPB and disease transmission modelling. Exp...

Influenza at the human-animal interface Summary and risk assessment, from 21 January to 19 March 2025 {1}  New human cases {2}:  From 21 January to 19 March 2025, based on reporting date , the detection of influenza A( H5N1 ) in five humans, influenza A( H9N2 ) virus in four humans, influenza A( H1N1 ) variant ((H1N1)v) virus in one human, and influenza A( H1N2 )v virus in one human were reported officially.  • 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}:  -- Sustained human to human transmission has not been reported from these events. Based on information available at the time of the risk assessmen...