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Showing posts with the label seasonal influenza

An #mRNA #influenza #vaccine induces #immunity comparable to an adjuvanted vaccine in a randomized trial

  Abstract Influenza causes substantial morbidity and mortality worldwide. This randomized, open-label, phase 1 trial (ClinicalTrials.gov, NCT05397223, date of registration: May 31, 2022) compared the immunogenicity of an mRNA-based quadrivalent influenza hemagglutinin (HA) vaccine (mRNA-1010) with a licensed comparator (FLUAD) in adults aged 18-75 years . We evaluated humoral and cellular immune responses using hemagglutination inhibition assays , flow cytometry-based memory B cell (MBC) profiling, and intracellular cytokine staining for T-cell characterization. Both vaccines elicited durable hemagglutination inhibition titers and increased HA-specific MBC responses across four vaccine strains. Compared with FLUAD, mRNA-1010 induced higher frequencies of classical and activated MBCs specific to the H3 HA included in the vaccine, while inducing similar MBC responses to the other strains. mRNA-1010 and FLUAD generated strong HA-specific CD4+ T-cell responses; a trend toward higher C...

#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...

Broadly neutralizing monoclonal #antibodies against #influenza A viruses: current #insights and future directions

  Abstract Monoclonal antibodies (mAbs) have become attractive tools for both the treatment and prevention of influenza A viruses due to their ability to target several viral components, which confers broad therapeutic potential. Advances in biotechnology, such as hybridoma technology , phage display technology , B cell immortalization , and artificial intelligence (Al)-driven antibody design, have significantly accelerated the development of effective mAbs. Clinical trials have shown that mAbs can improve clinical outcomes particularly in high-risk and immunocompromised populations by lowering viral loads and reducing disease severity. However, high production costs, the need for intravenous administration , and the risk of viral escape mutations are some of the obstacles to widespread clinical adoption. Post-marketing surveillance serves as a valuable source of information regarding safety, real-world effectiveness, and patterns of resistance. Broadly neutralizing antibodies (bnA...

#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, Jan. 11 '26)

  Ann Intern Med TERAN-PLASENCIA JM, Kalil AC In adults hospitalized with acute HF, predischarge influenza vaccination reduced a composite of mortality or readmission at 1 y. Ann Intern Med. 2026 Jan 6. doi: 10.7326/ANNALS-25-04799. PubMed           Abstract available TONG SYC, Gibney KB In older adults, high- vs. standard-dose influenza vaccine reduced hospitalization for influenza or pneumonia. Ann Intern Med. 2026 Jan 6. doi: 10.7326/ANNALS-25-05209. PubMed           Abstract available Arch Virol YAN Y, Pan Z, Mao L, Niu P, et al Genome surveillance of SARS-CoV-2 Omicron XBB subvariants in Wuhan in June 2023. Arch Virol. 2026;171:38. PubMed           Abstract available Biochem Biophys Res Commun HUANG A, Li C, Wu H, Sun W, et al Development of human single-domain antibodies against influenza based on NA-targeting IgG. Biochem Biophys Res Commun. 2026;798:153238...

#Haemagglutinin 162-164 #deletions enhance #influenza B/Victoria virus #fitness and #virulence in vivo

  Abstract Influenza B viruses cause substantial respiratory disease and seasonal outbreaks. Despite decades of circulation in humans , only the B/Victoria lineage persisted after the COVID-19 pandemic. Continual evolution has generated hemagglutinin deletion variants at residues 162-164 that drive successive epidemics , yet their functional consequences remain poorly understood. Using integrated phylodynamics and reverse genetics , we show that Clade V1A.1 viruses carrying a two-amino acid deletion exhibit enhanced replication and increased virulence compared with ancestral viruses lacking deletions. The recently prevailing Clade V1A.3 , which harbors a three-amino acid deletion together with the K136E substitution, has completely displaced V1A.1 and causes more severe disease in mice . Both clades bound efficiently to alpha 2-3 and 2-6 sialylated glycans and exhibited broad tolerance to acidic pH and elevated temperatures . These findings reveal that specific combinations of HA d...

Adjuvanted #influenza #vaccination increases pre-existing #H5N1 cross-reactive #antibodies

  Abstract Highly pathogenic H5N1 avian influenza viruses of clade 2.3.4.4b cause sporadic human infections and currently raise concerns about a new influenza pandemic . Heterogeneities in disease severity have been observed in the past and are reported among infected farm workers in the United States . These may be attributed to differences in pre-existing H5N1 cross-reactive antibodies . In this study, we characterize H5N1 cross-reactive antibody landscapes in the current population (#NCT05794412 and #NCT01022905) and assess the effect of AS03-adjuvanted pandemic H1N1 and non-adjuvanted seasonal influenza vaccination on H5N1 cross-neutralizing and IgG antibody titers targeting a range of influenza virus-derived antigens. We detect H5N1 cross-neutralizing antibodies using a vesicular stomatitis virus-based pseudovirus system that correlate well with antibodies inhibiting the spread of authentic H5N1 viruses, anti-group 1 hemagglutinin stalk and anti-trimeric hemagglutinin antibodi...

#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...

Intrahost HA #polymorphisms and culture #adaptation shape antigenic profiles of #H3N2 #influenza viruses

  ABSTRACT Accurate antigenic characterization of influenza viruses is critical for vaccine strain selection but is often confounded by intrahost genetic diversity and culture-induced adaptations . We analyzed 60 A(H3N2)-positive nasopharyngeal specimens collected during the 2017–2018 influenza season to determine how virus propagation in MDCK cells affects viral genetic and antigenic properties . Deep sequencing revealed frequent genome-wide intrahost polymorphisms , including amino acid variants within major hemagglutinin (HA) antibody-binding sites . Virus propagation imposed rapid purifying selection, markedly reducing intrahost genetic diversity . Serological analyses demonstrated that these selective events altered antigenic properties, indicating that culture adaptation can alter antigenic profiles . To assess the functional impact of HA polymorphisms, we generated mixed viral populations containing defined ratios of HA-160K, HA-160T, and HA-160I variants identified in clini...

T cell #immunity to seasonal #Influenza A and #H5N1 viruses in #laboratory #workers receiving annual seasonal Influenza #vaccines

  {Abstract} Background :  Emerging threats such as highly pathogenic influenza strains like H5N1 emphasize the need for vaccines that induce cross-reactive immunity against conserved epitopes. Existing influenza vaccines primarily elicit strain-specific responses , leaving gaps in protection against pandemic subtypes. This study aimed to evaluate T cell responses to seasonal influenza A and H5N1 and compare them to SARS-CoV-2 specific T cell responses to understand differences shaped by distinct exposure histories and vaccination strategies. Methods :  T cell responses were assessed in 41 laboratory workers who received annual seasonal influenza vaccines using ELISpot to quantify responses to peptide pools derived from influenza ( H1N1 hemagglutinin [HA], H3N2 HA, H5N1 HA, matrix protein 1 [MP1], nucleoprotein [NP]) and SARS-CoV-2 (spike [S2S], nucleocapsid [S2N]). Ten-day expansion assays were used to evaluate functional cross-reactivity between H1, H3, and H5 HA. Intra...

#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, Jan. 3 '26)

  BMC Pediatr CHEN Y, Wang Y, Tao X, Zhou M, et al Pediatric necrotizing pneumonia caused by mixed infection with influenza A virus and Panton-Valentine Leucocidin-producing Staphylococcus aureus: case report and literature review. BMC Pediatr. 2025 Dec 24. doi: 10.1186/s12887-025-06410. PubMed           Abstract available Eur J Epidemiol OSTERGREN OM, Counil E, Karimi A, Fall T, et al Who got tested and who got sick? Sociodemographic inequalities in COVID-19 testing and hospitalization among 1.48 million individuals in Sweden. Eur J Epidemiol. 2025;40:1431-1439. PubMed           Abstract available J Immunol ABE K, Holmes TH, Nguyen TT, Kim-Schulze S, et al Evaluating COVID-19 severity prediction and immune dynamics with NULISAseq: Insights from the IMPACC study. J Immunol. 2025;214:3310-3320. PubMed           Abstract available OSUAGWU AE, Payne M, Bosch J, Mbony...

#Coinfection of #SARS-CoV-2 and #Influenza: A Catastrophic Coexistence

  Abstract   SARS-CoV-2 is a major global public health burden associated with significant morbidity, mortality, and complications , including respiratory, cardiovascular, neurological , and digestive disorders. COVID-19 may induce venous and arterial thromboembolic complications , including deep vein thrombosis , myocardial infarction and cerebral infarction . Simultaneous myocardial and cerebral infarction, termed cardio-cerebral infarction , is exceedingly rare. There is only limited case of concurrent cardio-cerebral infarction in patients with COVID-19 . Although there is no standard treatment for the condition, antiplatelet and anticoagulation agents should be used. We emphasize the catastrophic coexistence of concurrent cardio-cerebral infarction in a patient co-infected with SARS-CoV-2 and influenza A. We described a 75-year-old woman was admitted for SARS-CoV-2 and influenza A coinfection . She received anti-viral agent treatment for the virus infection. The patient p...

#Influenza #vaccination post - #COVID19 expands vaccine-specific effector #CD4 T-cells and Tregs under positive influence of host trained innate #immunity

  Abstract SARS-CoV-2 immunity and innate immune training may influence influenza vaccine immunogenicity . We investigated this in India . Adult volunteers with hybrid SARS-CoV-2 immunity were administered FluarixTM Tetra (GlaxoSmithKlein) 2022/2023 NH Vaccine in 2022. Significant induction of hemagglutinin inhibition-specific antibodies and polyfunctional central memory CD4+ T-cells (TCM) were observed 1-week post-vaccination with variable induction of CD8+T-cell and innate effectors. Vaccination also expanded Flu-specific regulatory T-cells (Treg), which negatively correlated with CD4 responses , highlighting vaccine immunogenicity may be subject to Treg dampening . FluarixTM did not boost SARS-CoV-2 immunity . However, SARS-CoV-2 -specific T-cell responses correlated positively with vaccine-induced T-cell responses. We evaluated trained immunity post-COVID-19 as a potential regulatory mechanism linking SARS-CoV-2 and heterologous vaccine immunogenicity . We observed, elevated fr...

#Influenza PA #Substitutions and Genetic Diversity of #H1N1pdm09, #H3N2, and B/Victoria Viruses in #Japan During the 2023–2024 Season

  Abstract We characterized influenza A(H1N1)pdm09, A(H3N2), and B/Victoria viruses circulating in Japan during 2023–2024 , focusing on lineage placement relative to WHO-recommended vaccine strains and on baloxavir resistance (PA/I38T substitutions). We enrolled 210 outpatients with influenza-like illness across eight clinics in six prefectures (October 2023–September 2024). Of these, 209 had an analyzable pre-treatment respiratory specimen for RT-PCR; hemagglutinin (HA) and neuraminidase (NA) genes were sequenced by next-generation sequencing (NGS). PA/I38T substitutions that confer baloxavir resistance were assessed by cycling-probe RT-PCR, Sanger sequencing, and NGS. HA phylogenies were constructed with global datasets and WHO vaccine reference strains. Of 209 pre-treatment specimens, 181 were influenza-positive (A(H1N1)pdm09 44.2%, A(H3N2) 37.6%, B/Victoria 18.2%); 51 follow-up specimens were collected ≈4–5 days after baloxavir or neuraminidase inhibitor therapy . HA phylogeny ...

#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, Dec. 21 '25)

  Antimicrob Agents Chemother LEONARD VHJ, Vidales DB, Taft BR, Hesse MJ, et al Identification and characterization of a novel inhibitor of influenza A virus that acts by blocking nucleoprotein oligomerization. Antimicrob Agents Chemother. 2025 Dec 19:e0114925. doi: 10.1128/aac.01149. PubMed           Abstract available Arch Virol BEDAIR NM, Sakr MA, Mourad A, Eissa N, et al Genetic characterization of highly pathogenic avian influenza A/H5N8 virus isolated from commercial poultry farms in Egypt reveals zoonotic potential. Arch Virol. 2025;171:29. PubMed           Abstract available Biochemistry WESTMAN H, Hammarstrom P, Nystrom S SARS-CoV-2 Spike Protein Amyloid Fibrils Impair Fibrin Formation and Fibrinolysis. Biochemistry. 2025;64:4818-4829. PubMed           Abstract available Epidemiol Infect STADHOUDERS L, Hoogteijling EM, Duijts L, Lebon A, et al Trends in a...