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Showing posts with the label a/h3n2

#Vaccine-Elicited #Antibody Responses to #Influenza #H3N2 Subclade K

  {Excerpt} (...) Results NAb geometric mean titers against H1N1 WI/22, H3N2 BA/22, H3N2 CR/23, H3N2-K BA/25, and H3N2-K NY/25 were 200, 231, 119, 50, and 60 at baseline and increased to 582, 661, 356, 85, and 119 at peak immunogenicity, respectively (...), reflecting a significant 2.86- to 2.99-fold increase in NAb titers against the prior H1N1 and H3N2 strains but a lower 1.70- to 1.98-fold increase in NAb titers against the H3N2-K strains . Baseline antibody titers to the H3N2-K strains were 2.0- to 4.6-fold lower than to the prior H1N1 and H3N2 strains (P < .001), and peak antibody titers to the H3N2-K strains following vaccination were 3.0- to 7.8-fold lower than to the prior H1N1 and H3N2 strains (P < .001). (...) Source:  Link:  https://jamanetwork.com/journals/jama/fullarticle/2846268?guestAccessKey=10f1c0a1-4189-438d-9f71-a588fdd0db53&utm_medium=email&utm_source=postup_jn&utm_campaign=article_alert-jama&utm_content=olf-tfl_&utm_term=0309...

Recommended #composition of #influenza virus #vaccines for use in the 2026 – 2027 northern hemisphere influenza season (#WHO, Feb. 27 '26)

  February 2026  WHO convenes technical consultations {1} in February and September each year to recommend viruses for inclusion in influenza vaccines {2} for the northern hemisphere (NH) and southern hemisphere (SH) influenza seasons, respectively.  This recommendation relates to the influenza vaccines for use in the NH 2026-2027 influenza season .  A recommendation will be made in September 2026 relating to vaccines that will be used for the SH 2027 influenza season.  WHO guidance for choosing between the NH and SH formulations for countries in tropical and subtropical regions is available on the WHO Global Influenza Programme website {3}.   National or regional authorities approve the composition and formulation of influenza vaccines used in each country.  National public health authorities are responsible for making recommendations regarding the use of the vaccine.  WHO has published recommendations on the prevention of influenza {4}....

#Report on #influenza viruses received and tested by the #Melbourne #WHO CC for #Reference and Research on #Influenza during 2024

  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...

Evaluating #primer and #probe #mismatch tolerance in an #Influenza A #matrix gene RT #qPCR using contemporary human and zoonotic strains

  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...

Amino acid #mutations K54E and S154P in the #neuraminidase attenuate #H3N2 #canine #influenza virus in mice

  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 ...

Characterization of a reassortant #H3N2 swine #influenza virus with 2009 pandemic internal #genes and enhanced potential for zoonotic #risk

  Highlights •  A swine influenza virus H3N2 subtype was isolated during epidemiological survey. •  It is a complex and novel reassortant , and acquired accumulation of adaptive mutations. •  Both rescue and parent strains demonstrated efficient replication in mammalian cells. •  Key residues of the H3N2 HA collectively enhance the binding preference for human-type receptor. •  The rescued H3N2 cause significant pulmonary pathological damage in mice. Abstract Pigs serve as key "mixing vessels" for influenza A viruses, playing a critical role in cross-species transmission , while the H3N2 subtype represents an important lineage within the swine influenza virus (SIV) family. In this study, a novel reassortant H3N2 SIV strain , designated A/Swine/Jiangsu/YZ07/2024 , was isolated from pigs exhibiting clinical symptoms in Northern Jiangsu , China during epidemiological survey . Genetic analysis revealed that the virus is a complex reassortant, with the internal ...

Emergence and #antigenic characterisation of #influenza #H3N2 viruses with #hemagglutinin substitutions N158K and K189R during the 2024/25 influenza season

  Abstract Background   Seasonal human influenza viruses can escape from antibody-mediated neutralization when amino acid changes occur in the hemagglutinin protein . Routine surveillance identified circulation of an A(H3N2) virus variant in the Netherlands with amino acid substitutions at hemagglutinin positions 158 and 189 . These amino acid positions were previously responsible for antigenic change of influenza A(H3N2) viruses and potentially lead to escape of this variant from vaccine-mediated immunity .  Aim   To characterize the emergence and antigenic properties of N158K and K189R double substitution virus variants .  Methods   We analyzed the geographical and temporal dynamics of the double-substitution variant using a phylogeographic approach and used hemagglutination inhibition assays and antigenic cartography methods to map its antigenic properties.  Results   A(H3N2) viruses carrying K189R were first detected in Guatemala in June 2024,...

Impaired #host shutoff is a fitness cost associated with #baloxavir marboxil #resistance #mutations in #influenza A virus PA/PA-X nuclease domain

  Abstract The polymerase acidic (PA) protein is a subunit of the trimeric influenza A virus (IAV) RNA-dependent RNA polymerase and the target of the anti-influenza drug baloxavir marboxil (BXM). As with other direct-acting antivirals , treatment with BXM can lead to selection of viruses carrying resistance mutations . If these mutations have negligible fitness costs, resistant viruses can spread widely and render existing treatments obsolete . Multiple BXM resistance mutations in the nuclease domain of PA have been identified, with I38T and I38M amino acid substitutions occurring frequently. These mutations have minimal to no effects on viral polymerase activity , virus replication , or transmission . However, for reasons that are not well understood, viruses with BXM resistance substitutions have not been able to compete with parental wild-type strains . The IAV genome segment encoding PA also encodes the host shutoff nuclease PA-X, which shares the endonuclease domain with PA bu...

Genomic #Evolution of #Influenza A Virus During the 2024-2025 Season, the Johns Hopkins Health System: Antigenic Drift Reduces Serum Neutralization

  Abstract Introduction Seasonal influenza causes significant global morbidity, mortality, and economic burden . Ongoing viral evolution can lead to vaccine mismatch and the emergence of antiviral resistance , highlighting the importance of genomic surveillance. The 2024–2025 influenza season was characterized by high incidence and increased hospitalizations. Methods We analyzed influenza A virus (IAV) genomes and clinical characteristics from the 2024–2025 season . Whole-genome sequencing was performed on 648 influenza A–positive clinical specimens collected between October 2024 and April 2025. Results Hemagglutinin (HA) sequences were recovered from 74.23% (481/648) of samples and used for subtyping and phylogenetic analysis. A(H1N1)pdm09 and A(H3N2) viruses co-circulated , representing 55.5% and 44.5% of cases, respectively. Among A(H1N1)pdm09 viruses, the HA1 substitution T120A , located near the Sa antigenic site , increased more than twofold compared with the prior season. Ci...

#Antigenic #Drift and Antivaccine Shift in the 2025–2026 #Influenza Season

  {Summary} Recent headlines about influenza have reported a “super flu” causing a “record-breaking season” that is “overwhelming hospitals.” Although less dramatic, data from the Centers for Disease Control and Prevention (CDC) reveal substantial influenza activity : the agency estimated that there were more than 20 million cases of influenza illness, 270,000 influenza-related hospitalizations , and 11,000 deaths from influenza in the United States through January 24, 2026. These numbers aren’t extraordinary as compared with those from previous seasons, but some indicators of influenza activity and severity have been remarkable. (...) Source:  Link:  https://www.nejm.org/doi/full/10.1056/NEJMp2600395?query=TOC ____

Subclade K #influenza A #H3N2 viruses display partial immune #escape with preserved cross-neutralisation in a #UK population

  Abstract We examined whether the recent emergence of influenza A(H3N2) subclade K, associated with an unusually early influenza season in the Northern hemisphere, was accompanied by a reduction in human population immunity . Using virus neutralisation assays on pre-epidemic human sera collected in May 2025, we found evidence of moderate antigenic drift . Further, vaccines used in the 2024/2025 season induced cross-neutralising immunity . These findings provide timely insight for interpreting recent influenza epidemiology and informing vaccine strain selection. Competing Interest Statement The following authors declare no conflict of interests: KD, RI, LM, SR, HC, GGA, MSA, VS, ZW, SKW, JZ, BJW, DLR, JH, OML, JG, CJRI. PRM receives funding for research work for MSD. EH has received an honorarium for advisory board work for Seqirus. ET has received funding from Novavax and Astra Zeneca. Funding Statement This work was funded by the Medical Research Council (MRC) to the MRC-Universi...

#Molecular basis of 60 years of #antigenic #evolution of #human #influenza #H3N2 virus neuraminidase

  Highlights •  Human influenza A virus N2 neuraminidases were analyzed by antigenic cartography •  N2 antigenic evolution was discordant with antigenic evolution of H3 hemagglutinin •  Important epitopes were identified at the NA active site but also elsewhere in NA •  Changes in charge, volume, and hydropathy of epitope residues caused antigenic drift Summary Human influenza A viruses escape antibody-mediated immunity through changes in the hemagglutinin (HA) and neuraminidase (NA) glycoproteins . HA antigenic evolution has been studied extensively, with more recent interest in NA due to its importance in influenza vaccine efficacy. Here, the antigenic properties of the NA of more than 300 A( H3N2 ) and A( H2N2 ) viruses isolated since 1957 were quantified with a NA inhibition enzyme-linked lectin assay and visualized using antigenic cartography , with follow-up molecular studies using recombinant viruses. The antigenic evolution of N2 NA was more gradual than...

Within-host adaptive #evolution is limited by genetic #drift in experimental #human #influenza A virus #infections

  Abstract Selection of advantageous mutations drives the emergence of dominant variants during seasonal influenza epidemics . However, within-host detection of such variants remains rare , limiting our understanding of how selection operates at the scale of individual hosts. In this study, we used a controlled human infection model to examine the within-host evolutionary dynamics in thirteen participants intranasally infected with a seasonal H3N2 influenza A virus . Although this clinical trial is ongoing , our work represents a pre-planned, interim, exploratory analysis. Results in this system were contrasted with those observed in a ferret model of infection. The inoculum, used in both humans and ferrets, carried standing diversity that enabled evaluation of variant trajectories during infection. Although the dynamics were variable among participants, in humans , the minor variants in the PA and NP gene segments tended to increase in frequency as infection progressed. Variant dy...

#USA, #Massachusetts reports three #pediatric #deaths due to seasonal #influenza so far (DoH, Jan. 8 '26)

  Boston — The Massachusetts Department of Public Health (DPH) is reporting very high and rising levels of influenza activity statewide as the Commonwealth moves through peak flu season .  Thousands of residents have become ill , forcing them to miss work, school, and other activities.  Many are experiencing serious complications , leading to increased visits to urgent care centers and emergency departments, and high levels of hospitalization .  The current widespread burden of illness underscores the importance of taking preventive measures , especially vaccination , to reduce severe disease and protect individuals, families, and communities. Tragically, influenza has already been reported to be associated with the deaths of three pediatric patients in Massachusetts during recent weeks.  In addition, there have been 29 adult influenza deaths reported so far this season.  While COVID-19 and respiratory syncytial virus (RSV) rates currently remain low, cases...

#Adaptation differences and mechanisms of #influenza viruses to ANP32 #proteins across #species

  ABSTRACT Avian influenza virus cross-species infection in humans poses a major threat to global public health . Species-specific differences between avian ANP32A and mammalian ANP32 proteins create a natural barrier against viral cross-species infection by directly impairing the functional interaction between the avian-origin viral RNA polymerase and mammalian ANP32 proteins , thereby restricting viral genome replication . The key to overcoming this barrier lies in the adaptation of viral RNA polymerase to host ANP32 family proteins . This mini-review summarizes the mechanisms and variations in influenza virus adaptation to ANP32 proteins across different species. Influenza viruses adapt to species-specific ANP32 proteins through various mutations and display distinct preferences for specific ANP32 family members within the same host. Additionally, alternative splicing variants of ANP32A within a single species further modulate viral RNA polymerase adaptability. Despite this dive...