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Influenza hemagglutinin

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https://www.readbyqxmd.com/read/28332900/fc-or-not-fc-that-is-the-question-antibody-fc-receptor-interactions-are-key-to-universal-influenza-vaccine-design
#1
Sinthujan Jegaskanda, Hillary A Vanderven, Adam K Wheatley, Stephen J Kent
A universal vaccine that provides long-lasting protection from both epidemic and pandemic influenza viruses remains the "holy grail" of influenza vaccine research. Though virus neutralization assays are the current benchmark of measuring vaccine effectiveness, it is clear that Fc-receptor functions can drastically improve the effectiveness of antibodies and vaccines in vivo. Antibodies that kill virus-infected cells and/or elicit an antiviral environment, termed antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, provide a link between the innate and adaptive immune response...
March 23, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28331993/molecular-characterization-and-phylogenetic-analysis-of-human-influenza-a-viruses-isolated-in-iran-during-the-2014-2015-season
#2
Elham Moasser, Farida Behzadian, Afagh Moattari, Fatemeh Fotouhi, Amir Rahimi, Hassan Zaraket, Seyed Younes Hosseini
Influenza A viruses are an important cause of severe infectious diseases in humans and are characterized by their fast evolution rate. Global monitoring of these viruses is critical to detect newly emerging variants during annual epidemics. Here, we sought to genetically characterize influenza A/H1N1pdm09 and A/H3N2 viruses collected in Iran during the 2014-2015 influenza season. A total of 200 nasopharyngeal swabs were collected from patients with influenza-like illnesses. Swabs were screened for influenza A and B using real-time PCR...
March 22, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28331095/divergent-requirement-of-fc-fc%C3%AE-r-interactions-for-in-vivo-protection-against-influenza-viruses-by-two-pan-h5-hemagglutinin-antibodies
#3
Shuangshuang Wang, Huanhuan Ren, Wenbo Jiang, Honglin Chen, Hongxing Hu, Zhiwei Chen, Paul Zhou
Recent studies have shown that Fc-FcγR interactions are required for in vivo protection against influenza viruses by broadly reactive anti-HA stem, but not virus strain-specific, anti-receptor binding site (RBS), antibodies (Abs). Since only a few Abs recognizing epitopes in the head region but outside the RBS have been tested against single challenge virus strains, it remains unknown whether Fc-FcγR interactions are required for in vivo protection by Abs recognizing epitopes outside the RBS, and whether the requirement is virus strain-specific or epitope-specific...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28325769/analysis-of-anti-influenza-virus-neuraminidase-antibodies-in-children-adults-and-the-elderly-by-elisa-and-enzyme-inhibition-evidence-for-original-antigenic-sin
#4
Madhusudan Rajendran, Raffael Nachbagauer, Megan E Ermler, Paul Bunduc, Fatima Amanat, Ruvim Izikson, Manon Cox, Peter Palese, Maryna Eichelberger, Florian Krammer
Antibody responses to influenza virus hemagglutinin provide protection against infection and are well studied. Less is known about the human antibody responses to the second surface glycoprotein, neuraminidase. Here, we assessed human antibody reactivity to a panel of N1, N2, and influenza B virus neuraminidases in different age groups, including children, adults, and the elderly. Using enzyme-linked immunosorbent assays (ELISA), we determined the breadth, magnitude, and isotype distribution of neuraminidase antibody responses to historic, current, and avian strains, as well as to recent isolates to which these individuals have not been exposed...
March 21, 2017: MBio
https://www.readbyqxmd.com/read/28321412/recombinant-lactococcus-lactis-expressing-haemagglutinin-from-a-polish-avian-h5n1-isolate-and-its-immunological-effect-in-preliminary-animal-trials
#5
Agnieszka K Szczepankowska, Katarzyna Szatraj, Przemysław Sałański, Agnieszka Rózga, Roman K Górecki, Jacek K Bardowski
Lactic acid bacteria (LAB) are Gram-positive, nonpathogenic microorganisms that are gaining much interest as antigen producers for development of live vaccine vectors. Heterologous proteins of different origin have been successfully expressed in various LAB species, including Lactococcus lactis. Recombinant L. lactis strains have been shown to induce specific local and systemic immune responses against various antigens. Our study aimed at constructing a L. lactis strain expressing haemagglutinin of a Polish avian H5H1 influenza isolate and examining its effect on animals...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28320973/structure-of-the-infectious-salmon-anemia-virus-receptor-complex-illustrates-a-unique-binding-strategy-for-attachment
#6
Jonathan D Cook, Azmiri Sultana, Jeffrey E Lee
Orthomyxoviruses are an important family of RNA viruses, which include the various influenza viruses. Despite global efforts to eradicate orthomyxoviral pathogens, these infections remain pervasive. One such orthomyxovirus, infectious salmon anemia virus (ISAV), spreads easily throughout farmed and wild salmonids, constituting a significant economic burden. ISAV entry requires the interplay of the virion-attached hemagglutinin-esterase and fusion glycoproteins. Preventing infections will rely on improved understanding of ISAV entry...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28302407/immunogenicity-and-safety-of-an-as03-adjuvanted-h7n1-vaccine-in-adults-65years-of-age-and-older-a-phase-ii-observer-blind-randomized-controlled-trial
#7
Anuradha Madan, Murdo Ferguson, Paul Rheault, David Seiden, Azhar Toma, Damien Friel, Jyoti Soni, Ping Li, Bruce L Innis, Anne Schuind
BACKGROUND: H7 influenza strains can cause severe and often fatal human infections, especially in the elderly. This phase II, observer-blind, randomized trial (www.ClinicalTrials.gov: NCT01949090) assessed the immunogenicity and safety of a novel AS03-adjuvanted H7N1 vaccine that may serve as a model H7-subtype vaccine. METHODS: 360 adults ≥65years of age in stable health received either 1 of 4 adjuvanted A/mallard/Netherlands/12/2000 split virion vaccine formulations (3...
March 13, 2017: Vaccine
https://www.readbyqxmd.com/read/28301927/molecular-mechanism-underlying-the-action-of-the-influenza-a-virus-fusion-inhibitor-mbx2546
#8
Arnab Basu, Gloria Komazin-Meredith, Courtney McCarthy, Aleksandar Antanasijevic, Steven C Cardinale, Rama K Mishra, Dale L Barnard, Michael Caffrey, Lijun Rong, Terry L Bowlin
Influenza A virus envelop protein, Hemagglutinin (HA), plays important roles in viral entry. We previously have reported that MBX2546, a novel influenza A virus inhibitor, binds to HA and inhibits HA-mediated membrane fusion. In this report, we show that (i) both binding and stabilization of HA by MBX2546 is required for inhibition of viral infection, and (ii) binding of HA by MBX2546 represses the low-pH-induced conformational change of the HA which is a prerequisite for membrane fusion. Mutations in MBX2546-resistant influenza A/PR/8/34 (H1N1) viruses are mapped in the HA stem region near the amino terminus of HA2...
March 16, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28301280/panblok-h1-advax-h1n1-2009pdm-vaccine-insights-into-rapid-development-of-an-delta-inulin-adjuvanted-recombinant-pandemic-influenza-vaccine
#9
Yoshikazu Honda-Okubo, Harinda Rajapaksha, Dimitar Sajkov, David Gordon, Manon M J Cox, Nikolai Petrovsky
Timely vaccine supply is critical during influenza pandemics but is impeded by current virus-based manufacturing methods. The 2009 H1N1/2009pdm 'swine flu' pandemic reinforced the need for innovation in pandemic vaccine design. We report on insights gained during rapid development of a pandemic vaccine based on recombinant haemagglutinin (rHA) formulated with Advax™ delta inulin adjuvant (Panblok-H1/Advax). Panblok-H1/Advax was designed and manufactured within 1 month of the pandemic declaration by WHO and successfully entered human clinical testing in under 3 months from first isolation and sequencing of the novel pandemic virus, requiring several major challenges to be overcome...
February 14, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28301229/low-pathogenic-avian-influenza-viruses-in-wild-migratory-waterfowl-in-a-region-of-high-poultry-production-delmarva-maryland
#10
Diann J Prosser, Christine L Densmore, Larry J Hindman, Deborah D Iwanowicz, Chris A Ottinger, Luke R Iwanowicz, Cindy P Driscoll, Jessica L Nagel
Migratory waterfowl are natural reservoirs for low pathogenic avian influenza viruses (AIVs) and may contribute to the long-distance dispersal of these pathogens as well as spillover into domestic bird populations. Surveillance for AIVs is critical to assessing risks for potential spread of these viruses among wild and domestic bird populations. The Delmarva Peninsula on the east coast of the United States is both a key convergence point for migratory Atlantic waterfowl populations and a region with high poultry production (>4,700 poultry meat facilities)...
March 2017: Avian Diseases
https://www.readbyqxmd.com/read/28295019/m2e-tetramer-specific-memory-cd4-t-cells-are-broadly-protective-against-influenza-infection
#11
D G Eliasson, A Omokanye, K Schön, U A Wenzel, V Bernasconi, M Bemark, A Kolpe, K El Bakkouri, T Ysenbaert, L Deng, W Fiers, X Saelens, N Lycke
Matrix protein 2 ectodomain (M2e) is considered an attractive component of a broadly protective, universal influenza A vaccine. Here we challenge the canonical view that antibodies against M2e are the prime effectors of protection. Intranasal immunizations of Balb/c mice with CTA1-3M2e-DD-generated M2e-specific memory CD4 T cells that were I-A(d) restricted and critically protected against infection, even in the complete absence of antibodies, as observed in JhD mice. Whereas some M2e-tetramer-specific memory CD4 T cells resided in spleen and lymph nodes, the majority were lung-resident Th17 cells, that rapidly expanded upon a viral challenge infection...
March 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28292308/surveillance-of-avian-influenza-viruses-in-south-korea-between-2012-and-2014
#12
Eun-Kyoung Lee, Hyun-Mi Kang, Byung-Min Song, Yu-Na Lee, Gyeong-Beum Heo, Hee-Soo Lee, Youn-Jeong Lee, Jae-Hong Kim
BACKGROUND: National surveillance of avian influenza virus (AIV) in South Korea has been annually conducted for the early detection of AIV and responses to the introduction of highly pathogenic avian influenza (HPAI) virus. In this study, we report on a nationwide surveillance study of AIV in domestic poultry and wild birds in South Korea between 2012 and 2014. METHODS: During the surveillance programs between 2012 and 2014, 141,560 samples were collected. Of these, 102,199 were from poultry farms, 8215 were from LBMs, and 31,146 were from wild bird habitats...
March 14, 2017: Virology Journal
https://www.readbyqxmd.com/read/28291648/combining-stable-insect-cell-lines-with-baculovirus-mediated-expression-for-multi-ha-influenza-vlp-production
#13
Daniela P Sequeira, Ricardo Correia, Manuel J T Carrondo, António Roldão, Ana P Teixeira, Paula M Alves
Safer and broadly protective vaccines are needed to cope with the continuous evolution of circulating influenza virus strains and promising approaches based on the expression of multiple hemagglutinins (HA) in a virus-like particle (VLP) have been proposed. However, expression of multiple genes in the same vector can lead to its instability due to tandem repetition of similar sequences. By combining stable with transient expression systems we can rationally distribute the number of genes to be expressed per platform and thus mitigate this risk...
March 10, 2017: Vaccine
https://www.readbyqxmd.com/read/28288189/complete-mapping-of-viral-escape-from-neutralizing-antibodies
#14
Michael B Doud, Scott E Hensley, Jesse D Bloom
Identifying viral mutations that confer escape from antibodies is crucial for understanding the interplay between immunity and viral evolution. We describe a high-throughput approach to quantify the selection that monoclonal antibodies exert on all single amino-acid mutations to a viral protein. This approach, mutational antigenic profiling, involves creating all replication-competent protein variants of a virus, selecting with antibody, and using deep sequencing to identify enriched mutations. We use mutational antigenic profiling to comprehensively identify mutations that enable influenza virus to escape four monoclonal antibodies targeting hemagglutinin, and validate key findings with neutralization assays...
March 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28286060/a-broadly-reactive-human-anti-hemagglutinin-stem-monoclonal-antibody-that-inhibits-influenza-a-virus-particle-release
#15
Seiya Yamayoshi, Ryuta Uraki, Mutsumi Ito, Maki Kiso, Sumiho Nakatsu, Atsuhiro Yasuhara, Kohei Oishi, Tadahiro Sasaki, Kazuyoshi Ikuta, Yoshihiro Kawaoka
Many broadly reactive human monoclonal antibodies against the hemagglutinin (HA) stem of influenza A virus have been developed for therapeutic applications. These antibodies typically inhibit viral entry steps, especially the HA conformational change that is required for membrane fusion. To better understand the mechanisms by which such antibodies inhibit viral replication, we established broadly reactive human anti-HA stem antibodies and determined the properties of these antibodies by examining their reactivity with 18 subtypes of HA, evaluating their in vivo protective efficacy, identifying their epitopes, and characterizing their inhibitory mechanisms...
March 6, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28285982/evaluation-of-seasonal-influenza-vaccines-for-h1n1pdm09-and-type-b-viruses-based-on-a-replication-incompetent-pb2-ko-virus
#16
Hiroki Ui, Seiya Yamayoshi, Ryuta Uraki, Maki Kiso, Kohei Oishi, Shin Murakami, Shigetaka Mimori, Yoshihiro Kawaoka
Vaccination is the first line of protection against influenza virus infection in humans. Although inactivated and live-attenuated vaccines are available, each vaccine has drawbacks in terms of immunogenicity and safety. To overcome these issues, our group has developed a replication-incompetent PB2-knockout (PB2-KO) influenza virus that replicates only in PB2-expressing cells. Here we generated PB2-KO viruses possessing the hemagglutinin (HA) and neuraminidase (NA) segments from H1N1pdm09 or type B viruses and tested their vaccine potential...
March 9, 2017: Vaccine
https://www.readbyqxmd.com/read/28284616/mucosal-vaccination-of-conserved-sm2-ha2-and-cholera-toxin-subunit-a1-cta1-fusion-protein-with-poly-gamma-glutamate-chitosan-nanoparticles-pc-nps-induces-protection-against-divergent-influenza-subtypes
#17
Mohammed Y E Chowdhury, Tae-Hwan Kim, Md Bashir Uddin, Jae-Hoon Kim, C Y Hewawaduge, Zannatul Ferdowshi, Moon-Hee Sung, Chul-Joong Kim, Jong-Soo Lee
To develop a safe and effective mucosal vaccine that broad cross protection against seasonal or emerging influenza A viruses, we generated a mucosal influenza vaccine system combining the highly conserved matrix protein-2 (sM2), fusion peptide of hemagglutinin (HA2), the well-known mucosal adjuvant cholera toxin subunit A1 (CTA1) and poly-γ-glutamic acid (γ-PGA)-chitosan nanoparticles (PC NPs), which are safe, natural materials that are able to target the mucosal membrane as a mucosal adjuvant. The mucosal administration of sM2HA2CTA1/PC NPs could induce a high degree of systemic immunity (IgG and IgA) at the site of inoculation as well as at remote locations and also significantly increase the levels of sM2- or HA2-specific cell-mediated immune response...
March 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28282440/h1n1-influenza-viruses-varying-widely-in-hemagglutinin-stability-transmit-efficiently-from-swine-to-swine-and-to-ferrets
#18
Marion Russier, Guohua Yang, Atanaska Marinova-Petkova, Peter Vogel, Bryan S Kaplan, Richard J Webby, Charles J Russell
A pandemic-capable influenza virus requires a hemagglutinin (HA) surface glycoprotein that is immunologically unseen by most people and is capable of supporting replication and transmission in humans. HA stabilization has been linked to 2009 pH1N1 pandemic potential in humans and H5N1 airborne transmissibility in the ferret model. Swine have served as an intermediate host for zoonotic influenza viruses, yet the evolutionary pressure exerted by this host on HA stability was unknown. For over 70 contemporary swine H1 and H3 isolates, we measured HA activation pH to range from pH 5...
March 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28281252/plasmonics-based-detection-of-virus-using-sialic-acid-functionalized-gold-nanoparticles
#19
Changwon Lee, Peng Wang, Marsha A Gaston, Alison A Weiss, Peng Zhang
Biosensor for the detection of virus was developed by utilizing plasmonic peak shift phenomenon of the gold nanoparticles and viral infection mechanism of hemagglutinin on virus and sialic acid on animal cells. The plasmonic peak of the colloidal gold nanoparticles changes with the aggregation of the particles due to the plasmonic interaction between nearby particles and the color of the colloidal nanoparticle solution changes from wine red to purple. Sialic acid reduced and stabilized colloidal gold nanoparticle aggregation is induced by the addition of viral particles in the solution due to the hemagglutinin-sialic acid interaction...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28279563/a-small-molecule-irf3-agonist-functions-as-an-influenza-vaccine-adjuvant-by-modulating-the-antiviral-immune-response
#20
Peter Probst, John B Grigg, Myra Wang, Ernesto Muñoz, Yueh-Ming Loo, Renee C Ireton, Michael Gale, Shawn P Iadonato, Kristin M Bedard
Vaccine adjuvants are essential to drive a protective immune response in cases where vaccine antigens are weakly immunogenic, where vaccine antigen is limited, or where an increase in potency is needed for a specific population, such as the elderly. To discover novel vaccine adjuvants, we used a high-throughput screen (HTS) designed to identify small-molecule agonists of the RIG-I-like receptor (RLR) pathway leading to interferon regulatory factor 3 (IRF3) activation. RLRs are a group of cytosolic pattern-recognition receptors that are essential for the recognition of viral nucleic acids during infection...
March 6, 2017: Vaccine
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