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February 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 1 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 docume...

Highlights •  Scientific question :  Cross-species transmission of influenza A viruses from swine to humans occurs occasionally because their tracheal epitheliums possess both sialic acid α-2,6-Gal and α-2,3-Gal receptors . In 2011, the first human case of swine influenza virus infection in the mainland of China was detected in Jiangsu Province . Subsequently, the Eurasian avian-like H1N1 swine influenza virus (EAH1N1 SIV) had sporadically crossed the host barrier and infected humans, raising public concern for its pandemic potential. •  Evidence before this study :  A/Jiangsu/1/2011 (H1N1v) was first discovered in 2011 and belongs to the G1 genotype. The G4 and G5 genotypes that appeared successively in 2013 are recombinant H1N1 swine influenza viruses. The EAH1N1 SIVs from 2016 to the present are dominated by the G4 genotype, with hemagglutination (HA) and neuraminidase (NA) genes derived from the EAH1N1 SIVs, non-structural protein (NS) genes derived from the trip...

The World Health Organization (WHO) today announced the recommendations for the viral composition of influenza vaccines for the 2025-2026 influenza season in the northern hemisphere.  The announcement was made at an information session at the end of a 4-day meeting on the Composition of Influenza Virus Vaccines, a meeting that is held twice annually.  WHO organizes these consultations with an advisory group of experts gathered from WHO Collaborating Centres and WHO Essential Regulatory Laboratories to analyse influenza virus surveillance data generated by the WHO Global Influenza Surveillance and Response System (GISRS).  The recommendations issued are used by the national vaccine regulatory agencies and pharmaceutical companies to develop, produce, and license influenza vaccines for the following influenza season.  The periodic update of viruses contained in influenza vaccines is necessary for the vaccines to be effective due to the constant evolving nature of influ...

Abstract In 2018, a single detection of a novel reassortant swine influenza A virus (swIAV) was made in Denmark . The hemagglutinin (HA) of the virus was from the H1N1 pandemic 2009 (H1N1pdm09) lineage and the neuraminidase (NA) from the H1N1 Eurasian avian-like swine lineage (H1N1av). By 2022, the novel reassortant virus (H1pdm09N1av) constituted 27% of swIAVs identified through the Danish passive swIAV surveillance program . Sequencing detected two H1pdm09N1av genotypes; Genotype 1 contained an entire internal gene cassette of H1N1pdm09 origin, Genotype 2 differed by carrying an NS gene segment of H1N1av origin . The internal gene cassette of Genotype 2 became increasingly dominant, not only in the H1pdm09N1av population, but also in other Danish enzootic swIAV subtypes. Phylogenetic analysis of the HA genes from H1pdm09N1av viruses revealed a monophyletic source , a higher substitution rate compared to other H1N1pdm09 viruses and genetic differences with human seasonal and other swi...

Abstract Vaccination is a common influenza A virus (IAV) control strategy for pigs. Vaccine efficacy depends on strain cross-protection and effective vaccination program implementation. We evaluated a multi-faceted IAV vaccination strategy which included (a) monthly surveillance of pigs at weaning , (b) selection of epidemiologically relevant strains from farms under surveillance, (c) updating IAV strains in custom-made vaccines, and (d) seasonal mass vaccination with custom-made vaccines given to sows in 35 farrow-to-wean farms within an integrated swine farm system. Reduction of IAV in pigs from vaccinated sows was determined by monthly monitoring of farms for 30 months by IAV rRT-PCR (PCR) testing of nasal wipes collected from litters of piglets at weaning. Hemagglutinin (HA) nucleotide and amino acid (AA) sequence homology of the circulating and vaccine strains was determined by pairwise alignment and AA comparison at antigenic sites. Of the 35 farms monitored, 28 (80%) tested posi...

Abstract Influenza A viruses (IAV) are likely candidates for pandemics . This report summarizes the results of the Swiss national program for surveillance of influenza viruses in pigs and transmissions to humans between 2010 and 2022. Challenges and optimization options in the program are discussed. Nasal swabs or lung tissue samples from pigs with influenza-like signs (e.g. fever, cough) were screened by real-time RT-PCR for swine influenza virus (SIV) genomes, including that of the 2009 pandemic strain A(H1N1)pdm09; positive samples were subtyped for H1, N1, H3 and N2 by RT-PCR and Sanger sequencing. In parallel, humans with influenza-like symptoms and recent contact to diseased pigs were asked to self-sample themselves with a nasal swab. Human swabs were tested for IAV and positive swabs further subtyped to identify potential cross-species transmission between swine and humans. In the pigs, SIV was detected in 375 of 674 farm visits . H1N1 is the only subtype detected in Swiss pigs ...

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...

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...

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 ...

Abstract The Eurasian avian-like (EA) H1N1 swine influenza virus (SIV) possesses the capacity to instigate the next influenza pandemic , owing to its heightened affinity for the human-type α-2,6 sialic acid (SA) receptor . Nevertheless, the molecular mechanisms underlying the switch in receptor binding preferences of EA H1N1 SIV remain elusive. In this study, we conduct a comprehensive genome-wide CRISPR/Cas9 knockout screen utilizing EA H1N1 SIV in porcine kidney cells. Knocking out the enzyme gamma glutamyl carboxylase (GGCX) reduces virus replication in vitro and in vivo by inhibiting the carboxylation modification of viral haemagglutinin (HA) and the adhesion of progeny viruses, ultimately impeding the replication of EA H1N1 SIV. Furthermore, GGCX is revealed to be the determinant of the D225E substitution of EA H1N1 SIV, and GGCX-medicated carboxylation modification of HA 225E contributes to the receptor binding adaption of EA H1N1 SIV to the α-2,6 SA receptor. Taken together, our...

Abstract Crocodilians are susceptible to a range of virus infection including influenza A virus (IAV). However, little is known about the ecology and epidemiology of IAV in crocodile species. This study aimed to investigate IAV infection in farmed Siamese crocodiles in central Thailand . We collected plasma samples and pharyngeal swab samples from Siamese crocodiles residing in 13 crocodile farms in 9 provinces of central Thailand during 2019. Additional archival plasma samples of Siamese crocodiles collected in 2012 and 2018 were also included in the study. Plasma samples were screened for influenza A antibodies by a hemagglutination inhibition (HI) assay and positive were evaluated by a cytopathic effect/hemagglutination based- microneutralization (MN) assay . Swab samples were tested for influenza viral RNA by a real-time RT-PCR assay targeting the influenza matrix (M) gene. Among 246 tested plasma samples, the overall seroprevalence of antibodies against IAV in farmed Siamese croco...

Abstract East, South, and Southeast Asia (together referred to as Southeastern Asia hereafter) have been recognized as critical areas fuelling the global circulation of seasonal influenza . However, the seasonal influenza migration network within Southeastern Asia remains unclear, including how pandemic-related disruptions altered this network. We leveraged genetic, epidemiological, and airline travel data between 2007-2023 to characterise the dispersal patterns of influenza A/H3N2 and B/Victoria viruses both out of and within Southeastern Asia, including during perturbations by the 2009 A/H1N1 and COVID-19 pandemics. During the COVID-19 pandemic , consistent autumn-winter movement waves from Southeastern Asia to temperate regions were interrupted for both subtype/lineages, however the A/H1N1 pandemic only disrupted A/H3N2 spread . We find a higher persistence of A/H3N2 than B/Victoria circulation in Southeastern Asia and identify distinct pandemic-related disruptions in A/H3N2 antigen...

Abstract Zoonotic infections (swine-human) caused by influenza A viruses (IAVs) have been reported and linked to close contact between these species . Here, we describe eight human IAV variant infections ( 6 mild and 2 severe cases , including 1 death ) detected in Paraná, Brazil , during 2020–2023. Genomes recovered were closely related to Brazilian swIAVs of three major lineages (1 A.3.3.2/ pdm09, 1B/human-like, and H3.1990.5), including three H1N1v, two H1N2v, two H3N2v and one H1v. Five H1v were closely related to pdm09 lineage , one H1v ( H1N2v ) grouped within 1B.2.3 clade, and the two H3v grouped within a clade composed exclusively of Brazilian H3 swIAV (clade H3.1990.5.1). Internal gene segments were closely related to H1N1pdm09 isolated from pigs . IAV variant rarely result in sustained transmission between people, however the potential to develop such ability is of concern and must not be underestimated. This study brings into focus the need for continuous influenza surveilla...

{Excerpt} In the 52nd week of 2024 ( December 23rd to December 29th ), respiratory samples from outpatient influenza-like cases and hospitalized severe acute respiratory infection cases collected in sentinel hospitals across the country (excluding Hong Kong, Macao and Taiwan) were tested for 10 viruses including the new coronavirus, influenza virus, respiratory syncytial virus, adenovirus, human metapneumovirus, parainfluenza virus, common coronavirus, bocavirus, rhinovirus and enterovirus , as well as multiple respiratory pathogens including Mycoplasma pneumoniae. 1. Test results The pathogens detected positive in respiratory samples of influenza-like cases in outpatient and emergency departments of sentinel hospitals were mainly influenza virus, human metapneumovirus, and rhinovirus ; the pathogens detected positive in respiratory samples of hospitalized severe acute respiratory infection cases were mainly influenza virus, Mycoplasma pneumoniae, and human metapneumovirus . The specif...

 {Summary} Swine influenza virus (SIV) is a highly contagious pathogen that poses significant economic challenges to the swine industry and carries zoonotic potential , underscoring the need for vigilant surveillance. In this study, we performed a comprehensive genetic and molecular analysis of H3N2 SIV isolates obtained from 372 swine samples collected in Shandong Province, China . Phylogenetic analysis revealed two distinct genotypes . The surface genes of both genotypes clustered with the human-like H3N2 lineage , while the internal genes of one genotype clustered with the 2009 pandemic H1N1 (pdm/09) lineage . In the second genotype, the NS gene clustered with the classical swine (CS) H1N1 lineage , while the remaining internal genes clustered with pdm/09, suggesting stable integration of pdm/09 gene segments into H3N2 SIV. Homology analysis showed over 96% genetic similarity between the isolates and reference strains from China and Brazil , suggesting potential transmission thr...

Highlights -- Both NA-specific antibodies and memory B cells are detected in healthy adults -- NA broad-inhibition monoclonal antibodies are derived from classical memory B cells -- Broad inhibition monoclonal antibodies target the NA conserved enzymatic epitopes -- NA broad-inhibition antibodies protect mice against H1N1 and H5N1- clade 2.3.4.4b Summary Identifying broadly reactive B precursor cells and conserved epitopes is crucial for developing a universal flu vaccine . In this study, using influenza neuraminidase (NA) mutant probes , we find that human pre-existing NA-specific memory B cells (MBCs) account for ∼0.25% of total MBCs, which are heterogeneous and dominated by class-unswitched MBCs. In addition, we identify three NA broad-inhibition monoclonal antibodies (mAbs) (BImAbs) that block the activity of NA derived from different influenza strains, including the recent cow H5N1. The cryoelectron microscopy (cryo-EM) structure shows that the BImAb targets the conserved NA enzym...

Natalia A. Ilyushina {a b}, Nicolai V. Bovin {c}, Robert G. Webster {a d}, Elena A. Govorkova  {a b} a} Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794, USA; b} The D.I. Ivanovsky Institute of Virology, Gamaleya 16, Moscow 123098, Russia; c} Shemyakin Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya, Moscow 117997, Russia; d} Department of Pathology, University of Tennessee, Memphis, TN 38105, USA Received 21 November 2005, Accepted 26 January 2006, Available online 21 February 2006. Abstract Rapid development of resistant influenza variants after amantadine treatment is one of the main drawbacks of M2 blockers . On the other hand, the emergence of variants with low susceptibility to the neuraminidase (NA) inhibitors is limited. In the present study we examined whether combination therapy with two classes of anti-influenza drugs can affect the emergence of resistant variants in vitro. We observed that viru...

Abstract Influenza, a highly contagious respiratory infectious disease caused by an influenza virus , is a threat to public health worldwide . Avian influenza viruses (AIVs) have the potential to cause the next pandemic by crossing the species barrier through mutation of viral genome. Here, we investigated the pathogenicity of AIVs obtained from South Korea and Mongolia during 2018–2019 by measuring viral titers in the lungs and extrapulmonary organs of mouse models . In addition, we assessed the pathogenicity of AIVs in ferret models . Moreover, we compared the ability of viruses to replicate in mammalian cells , as well as the receptor-binding preferences of AIV isolates. Genetic analyses were finally performed to identify the genetic relationships and amino acid substitutions between viral proteins during mammalian adaptation. Of the 24 AIV isolates tested, A/Mallard/South Korea/KNU2019-34/2019 (KNU19-34; H1N1) caused severe bodyweight loss and high mortality in mice . The virus rep...

ABSTRACT The highly pathogenic avian influenza virus A(H5N1) clade 2.3.4.4b has caused a human outbreak in North America since March 2024 . Here, we conducted a serosurveillance study to determine the risk of A(H5N1) clade 2.3.4.4b (2024 cattle H5N1 ) to general population . In the initial screening of 180 serum specimens encompassing all age groups , 2.2% (4/180) had detectable neutralizing antibody (nAb) titers against 2024 cattle H5N1, with all collected from older adults aged ≥60 years old . Further screening showed that 5.0% (15/300) of adults aged ≥70 years old had detectable nAb titers against the 2024 cattle H5N1. All serum specimens with nAb titer of ≥40 had detectable HI titer, and there was a positive correlation between nAb titer and HA binding (r=0.3311, 95% confidence interval 0.2264 to 0.4283; P<0.0001). The nAb titer against seasonal H1N1 virus was 3.9-fold higher for patients with detectable H5N1 nAb than those without (geometric mean titer: 108.5 [95% CI 56.3-209.1...

Abstract Influenza A is a zoonotic disease that affects dogs, pigs, horses, poultry, and birds . In this report, a meta-analysis according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) was conducted. Studies of influenza A viruses in dogs providing prevalence or seroprevalence in any location worldwide were included. The results in this study show that the seroprevalence for the H3N8 influenza subtype was 7.96% (95% CI: 2.03–16.8, p < 0.001), for the H3N2 subtype was 7.44% (95% CI: 4.51–10.5, p < 0.001), and for the H1N1 subtype was 3.10% (95% CI: 0.890–6.01, p < 0.001). In the case of the prevalence analysis, a prevalence of 0.395% (95% CI: 0.160–2.44) for the H3N8 subtype. For the H3N2 subtype, a prevalence of 17.8% (95% CI: 6.66–32.6, p < 0.001) was found. No publication bias was observed in the studies evaluating seroprevalence in the H3N2 and H1N1 subtypes. In the H3N8 subtype, Begg’s test indicated publication bias, but Egger’s test sh...