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Influenza hemagglutinin

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https://www.readbyqxmd.com/read/28740382/dual-linker-gold-nanoparticles-as-adjuvanting-carriers-for-multivalent-display-of-recombinant-influenza-hemagglutinin-trimers-and-flagellin-improve-the-immunological-responses-in-vivo-and-in-vitro
#1
Chao Wang, Wandi Zhu, Bao-Zhong Wang
Vaccination is the most cost-effective means of infectious disease control. Although current influenza vaccines are effective in battling closely matched strains, such vaccines have major limitations such as the requirement to produce new vaccines every season, an egg-dependent production system, long production periods, uncertainty in matching the vaccine to circulating strains, and the inability to react to new influenza pandemics resulting from genetic drift or shift. To overcome the intrinsic limitations of the conventional influenza vaccine, we have designed dual-linker gold nanoparticles (AuNPs) conjugated with both recombinant trimetric A/Aichi/2/68 (H3N2), hemagglutinin (HA) and TLR5 agonist flagellin (FliC) as a novel vaccine approach...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28739603/novel-in-vitro-booster-vaccination-to-rapidly-generate-antigen-specific-human-monoclonal-antibodies
#2
Irene Sanjuan Nandin, Carol Fong, Cecilia Deantonio, Juan A Torreno-Pina, Simone Pecetta, Paula Maldonado, Francesca Gasparrini, Jose Ordovas-Montanes, Samuel W Kazer, Svend Kjaer, Daryl W Borley, Usha Nair, Julia A Coleman, Daniel Lingwood, Alex K Shalek, Eric Meffre, Pascal Poignard, Dennis R Burton, Facundo D Batista
Vaccines remain the most effective tool to prevent infectious diseases. Here, we introduce an in vitro booster vaccination approach that relies on antigen-dependent activation of human memory B cells in culture. This stimulation induces antigen-specific B cell proliferation, differentiation of B cells into plasma cells, and robust antibody secretion after a few days of culture. We validated this strategy using cells from healthy donors to retrieve human antibodies against tetanus toxoid and influenza hemagglutinin (HA) from H1N1 and newly emergent subtypes such as H5N1 and H7N9...
July 24, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28738896/real-time-reverse-transcription-pcr-based-sequencing-independent-pathotyping-of-eurasian-avian-influenza-a-viruses-of-subtype-h7
#3
Annika Graaf, Martin Beer, Timm Harder
Low pathogenic avian influenza viruses (LPAIV) of the subtypes H5 and H7 are known to give rise to highly pathogenic (HP) phenotypes by spontaneous insertional mutations which convert a monobasic trypsin-sensitive endoproteolytical cleavage site (CS) within the hemagglutinin (HA) protein into a polybasic subtilisin-sensitive one. Sporadic outbreaks of notifiable LPAIV H7 infections are continuously recorded in Europe and in Asia, and some lineages showed zoonotic transmission. De novo generation of HPAIV H7 from LPAIV precursors has been reported several times over the past decade...
July 24, 2017: Virology Journal
https://www.readbyqxmd.com/read/28730155/surveillance-study-of-influenza-occurrence-and-immunity-in-a-wisconsin-cohort-during-the-2009-pandemic
#4
Chia-Yun Lo, Susan L Strobl, Kimberly Dunham, Wei Wang, Lucy Stewart, Julia A Misplon, Mayra Garcia, Jin Gao, Tatsuhiko Ozawa, Graeme E Price, Jose Navidad, Steve Gradus, Sanjib Bhattacharyya, Cecile Viboud, Maryna C Eichelberger, Carol D Weiss, Jack Gorski, Suzanne L Epstein
BACKGROUND: Antibody and T-cell immunity to conserved influenza virus antigens can protect animals against infection with diverse influenza strains. Although immunity against conserved antigens occurs in humans, whether such responses provide cross-protection in humans and could be harnessed as the basis for universal influenza vaccines is controversial. The 2009 pandemic provided an opportunity to investigate whether pre-existing cross-reactive immunity affected susceptibility to infection...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28729956/predicting-the-host-of-influenza-viruses-based-on-the-word-vector
#5
Beibei Xu, Zhiying Tan, Kenli Li, Taijiao Jiang, Yousong Peng
Newly emerging influenza viruses continue to threaten public health. A rapid determination of the host range of newly discovered influenza viruses would assist in early assessment of their risk. Here, we attempted to predict the host of influenza viruses using the Support Vector Machine (SVM) classifier based on the word vector, a new representation and feature extraction method for biological sequences. The results show that the length of the word within the word vector, the sequence type (DNA or protein) and the species from which the sequences were derived for generating the word vector all influence the performance of models in predicting the host of influenza viruses...
2017: PeerJ
https://www.readbyqxmd.com/read/28729020/purification-of-cell-culture-derived-influenza-a-virus-via-continuous-anion-exchange-chromatography-on-monoliths
#6
Laura M Fischer, Michael W Wolff, Udo Reichl
The continuously increasing demand for potent and safe vaccines and the intensifying economic pressure on health care systems underlines the need for further optimization of vaccine manufacturing. Here, we focus on downstream processing of human influenza vaccines, investigating the purification of serum-free cell culture-derived influenza virus (A/PR/8/34 H1N1) using continuous chromatography. Therefore, quaternary amine anion exchange monoliths (CIM® QA) were characterized for their capacity to capture virus particles from animal cells cultivated in different media and their ability to separate virions from contaminating host cell proteins and DNA...
July 17, 2017: Vaccine
https://www.readbyqxmd.com/read/28724768/synthetic-tlr4-and-tlr7-ligands-work-additively-via-myd88-to-induce-protective-antiviral-immunity-in-mice
#7
Peter H Goff, Tomoko Hayashi, Wenqian He, Shiyin Yao, Howard B Cottam, Gene S Tan, Brian Crain, Florian Krammer, Karen Messer, Minya Pu, Dennis A Carson, Peter Palese, Maripat Corr
We have previously demonstrated that the combination of synthetic small molecule Toll-like receptor 4 (TLR4) and TLR7 ligands is a potent adjuvant for recombinant influenza virus hemagglutinin, inducing rapid and sustained immunity protective against influenza viruses in homologous, heterologous and heterosubtypic murine challenge models. Combining TLR4 and TLR7 ligands balances Th1/Th2-type immune responses for long-lived cellular and neutralizing humoral immunity against the viral hemagglutinin. Here, we demonstrate that the protective response induced in mice by this combined adjuvant is dependent upon TLR4 and TLR7 signaling via myeloid differentiation primary response gene 88 (MyD88), indicating that the adjuvants function in vivo via their known receptors with negligible off-target effects to induce protective immunity...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28724579/novel-bivalent-viral-vectored-vaccines-induce-potent-humoral-and-cellular-immune-responses-conferring-protection-against-stringent-influenza-a-virus-challenge
#8
Claire M Tully, Senthil Chinnakannan, Caitlin E Mullarkey, Marta Ulaszewska, Francesca Ferrara, Nigel Temperton, Sarah C Gilbert, Teresa Lambe
Seasonal influenza viruses are a common cause of acute respiratory illness worldwide and generate a significant socioeconomic burden. Influenza viruses mutate rapidly, necessitating annual vaccine reformulation because traditional vaccines do not typically induce broad-spectrum immunity. In addition to seasonal infections, emerging pandemic influenza viruses present a continued threat to global public health. Pandemic influenza viruses have consistently higher attack rates and are typically associated with greater mortality compared with seasonal strains...
July 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28723950/high-affinity-anti-tim-3-and-anti-kir-monoclonal-antibodies-cloned-from-healthy-human-individuals
#9
Stefan Ryser, Angeles Estellés, Edgar Tenorio, Lawrence M Kauvar, Mikhail L Gishizky
We report here the cloning of native high affinity anti-TIM-3 and anti-KIR IgG monoclonal antibodies (mAbs) from peripheral blood mononuclear cells (PBMC) of healthy human donors. The cells that express these mAbs are rare, present at a frequency of less than one per 105 memory B-cells. Using our proprietary multiplexed screening and cloning technology CellSpot™ we assessed the presence of memory B-cells reactive to foreign and endogenous disease-associated antigens within the same individual. When comparing the frequencies of antigen-specific memory B-cells analyzed in over 20 screening campaigns, we found a strong correlation of the presence of anti-TIM-3 memory B-cells with memory B-cells expressing mAbs against three disease-associated antigens: (i) bacterial DNABII proteins that are a marker for Gram negative and Gram positive bacterial infections, (ii) hemagglutinin (HA) of influenza virus and (iii) the extracellular domain of anaplastic lymphoma kinase (ALK)...
2017: PloS One
https://www.readbyqxmd.com/read/28720281/evaluation-of-a-primary-course-of-h9n2-vaccine-with-or-without-as03-adjuvant-in-adults-a-phase-i-ii-randomized-trial
#10
Anuradha Madan, Harry Collins, Eric Sheldon, Louise Frenette, Laurence Chu, Damien Friel, Mamadou Drame, David W Vaughn, Bruce L Innis, Anne Schuind
BACKGROUND: Avian influenza A H9N2 strains have pandemic potential. METHODS: In this randomized, observer-blind study (ClinicalTrials.gov: NCT01659086), 420 healthy adults, 18-64years of age, received 1 of 10 H9N2 inactivated split-virus vaccination regimens (30 participants per group), or saline placebo (120 participants). H9N2 groups received 2 doses (days 0, 21) of 15µg hemagglutinin (HA) without adjuvant, or 1.9µgHA+AS03A, 1.9µgHA+AS03B, 3.75µgHA+AS03A, or 3...
July 15, 2017: Vaccine
https://www.readbyqxmd.com/read/28715468/heterosubtypic-cross-reactivity-of-ha1-antibodies-to-influenza-a-with-emphasis-on-nonhuman-subtypes-h5n1-h7n7-h9n2
#11
Dennis E Te Beest, Erwin de Bruin, Sandra Imholz, Marion Koopmans, Michiel van Boven
Epidemics of influenza A vary greatly in size and age distribution of cases, and this variation is attributed to varying levels of pre-existing immunity. Recent studies have shown that antibody-mediated immune responses are more cross-reactive than previously believed, and shape patterns of humoral immunity to influenza A viruses over long periods. Here we quantify antibody responses to the hemagglutinin subunit 1 (HA1) across a range of subtypes using protein microarray analysis of cross-sectional serological surveys carried out in the Netherlands before and after the A/2009 (H1N1) pandemic...
2017: PloS One
https://www.readbyqxmd.com/read/28715148/lineage-specific-epitope-profiles-for-hpai-h5-pre-pandemic-vaccine-selection-and-evaluation
#12
Xueting Qiu, Venkata R Duvvuri, Jonathan B Gubbay, Richard Webby, Ghazi Kayali, Justin Bahl
BACKGROUND: Multiple highly pathogenic avian influenza (HPAI) H5 viruses continue to co-circulate. This has complicated pandemic preparedness and confounded effective vaccine candidate selection and evaluation. OBJECTIVES: In this study we aim to predict and map the diversity of CD8+ T-cell epitopes among H5 Hemagglutinin (HA) gene lineages to estimate CD8+ T-cell immunity in humans induced by vaccine candidates. METHODS: A dataset consisting of 1125 H5 HA sequences collected between 1996 and 2017 from avian and humans was assembled for phylogenetic and lineage-specific epitope analyses...
July 17, 2017: Influenza and Other Respiratory Viruses
https://www.readbyqxmd.com/read/28714909/the-interplay-between-the-host-receptor-and-influenza-virus-hemagglutinin-and-neuraminidase
#13
REVIEW
Lauren Byrd-Leotis, Richard D Cummings, David A Steinhauer
The hemagglutinin (HA) and neuraminidase (NA) glycoproteins of influenza A virus are responsible for the surface interactions of the virion with the host. Entry of the virus is mediated by functions of the HA: binding to cellular receptors and facilitating fusion of the virion membrane with the endosomal membrane. The HA structure contains receptor binding sites in the globular membrane distal head domains of the trimer, and the fusion machinery resides in the stem region. These sites have specific characteristics associated with subtype and host, and the differences often define species barriers...
July 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28712489/plant-made-virus-like-particles-bearing-influenza-hemagglutinin-ha-recapitulate-early-interactions-of-native-influenza-virions-with-human-monocytes-macrophages
#14
Alexander I Makarkov, Sabrina Chierzi, Stéphane Pillet, Keith K Murai, Nathalie Landry, Brian J Ward
INTRODUCTION: Plant-made virus-like particles (VLP) bearing influenza virus hemagglutinins (HA) are novel vaccine candidates that induce cross-reactive humoral and poly-functional T cell responses. To better understand the mechanisms that underlie this broad immunogenicity we studied early interactions of VLPs bearing either H1 (A/California/07/2009 (H1N1)) or H5 (A/Indonesia/05/2005 (H5N1)) with a human monocytoid cell line (U-937 cells) and human monocyte-derived macrophages (MDMs) as model antigen-presenting cells (APC)...
July 13, 2017: Vaccine
https://www.readbyqxmd.com/read/28710829/spatiotemporal-evolutionary-epidemiology-of-h5n1-highly-pathogenic-avian-influenza-in-west-africa-and-nigeria-2006-2015
#15
P S Ekong, N M Fountain-Jones, M A Alkhamis
H5N1 highly pathogenic avian influenza virus (HPAIV) was first observed in Nigeria in early 2006 and has now spread to more than 17 African countries having severe economic and public health implications. Here, we explore the spatiotemporal patterns of viral dispersal both among West African countries and within Nigeria using sequence data from hemagglutinin (HA) gene region of the virus. Analyses were performed within a statistical Bayesian framework using phylodynamic models on data sets comprising of all publically available HA sequence data collected from seven West African countries and Egypt between 2006 and 2015...
July 14, 2017: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/28709460/semi-quantitative-influenza-a-population-averages-from-a-multiplex-respiratory-viral-panel-rvp-potential-for-reflecting-target-sequence-changes-affecting-the-assay
#16
Kenneth H Rand, Maura Pieretti, Rodney Arcenas, Stacy G Beal, Herbert Houck, Emma Boslet, John A Lednicky
BACKGROUND: Yearly influenza virus mutations potentially affect the performance of molecular assays, if nucleic acid changes involve the sequences in the assay. Because individual patient viral loads depend on variables such as duration of illness, specimen type, age, and immunosuppression, we examined seasonal population averages of positive tests to smooth inherent variability. METHODS: We studied the population seasonal averages of the semi-quantitative nAMPs for the influenza matrix and hemagglutinin genes in the GenMark (Carlsbad, CA) Respiratory Viral Panel assay between 3 institutions over 3 Influenza seasons...
July 14, 2017: Virology Journal
https://www.readbyqxmd.com/read/28708860/charged-amino-acid-variability-related-to-n-glyco-sylation-and-epitopes-in-a-h3n2-influenza-hem-agglutinin-and-neuraminidase
#17
Zhong-Zhou Huang, Liang Yu, Ping Huang, Li-Jun Liang, Qing Guo
BACKGROUND: The A/H3N2 influenza viruses circulated in humans have been shown to undergo antigenic drift, a process in which amino acid mutations result from nucleotide substitutions. There are few reports regarding the charged amino acid mutations. The purpose of this paper is to explore the relations between charged amino acids, N-glycosylation and epitopes in hemagglutinin (HA) and neuraminidase (NA). METHODS: A total of 700 HA genes (691 NA genes) of A/H3N2 viruses were chronologically analyzed for the mutational variants in amino acid features, N-glycosylation sites and epitopes since its emergence in 1968...
2017: PloS One
https://www.readbyqxmd.com/read/28700751/a-high-seroprevalence-of-antibodies-to-pertussis-toxin-among-japanese-adults-qualitative-and-quantitative-analyses
#18
Takumi Moriuchi, Nao Otsuka, Yukihiro Hiramatsu, Keigo Shibayama, Kazunari Kamachi
In 2013, national serosurveillance detected a high seroprevalence of antibodies to pertussis toxin (PT) from Bordetella pertussis among Japanese adults. Thus, we aimed to determine the cause(s) of this high seroprevalence, and analyzed the titers of antibodies to PT and filamentous hemagglutinin (FHA) among adults (35-44 years old), young children (4-7 years old), and older children (10-14 years old). Our quantitative analyses revealed that adults had higher seroprevalences of anti-PT IgG and PT-neutralizing antibodies, and similar titers of anti-FHA IgG, compared to the young and older children...
2017: PloS One
https://www.readbyqxmd.com/read/28700738/age-dependent-differences-in-the-kinetics-of-%C3%AE-%C3%AE-t-cells-after-influenza-vaccination
#19
Ulrik Stervbo, Dominika Pohlmann, Udo Baron, Cecilia Bozzetti, Karsten Jürchott, Julia Nora Mälzer, Mikalai Nienen, Sven Olek, Toralf Roch, Axel Ronald Schulz, Sarah Warth, Avidan Neumann, Andreas Thiel, Andreas Grützkau, Nina Babel
Immunosenescence is a hallmark of the aging immune system and is considered the main cause of a reduced vaccine efficacy in the elderly. Although γδ T cells can become activated by recombinant influenza hemagglutinin, their age-related immunocompetence during a virus-induced immune response has so far not been investigated. In this study we evaluate the kinetics of γδ T cells after vaccination with the trivalent 2011/2012 northern hemisphere seasonal influenza vaccine. We applied multi-parametric flow cytometry to a cohort of 21 young (19-30 years) and 23 elderly (53-67 years) healthy individuals...
2017: PloS One
https://www.readbyqxmd.com/read/28700265/safety-and-immunogenicity-of-a-quadrivalent-influenza-vaccine-in-adults-65%C3%A2-years-of-age-and-older
#20
David P Greenberg, Corwin A Robertson, H Keipp Talbot, Michael D Decker
Frequent mismatches between the predominant circulating B strain lineage and the B strain lineage in trivalent influenza vaccines have resulted in missed opportunities to prevent influenza illness. Quadrivalent influenza vaccines containing B strains from each of the two lineages have been developed for improved prevention of influenza B infections. Here, we describe the results of a phase III, randomized, double-blind, active-controlled, multicenter trial examining the safety and immunogenicity of a split-virion inactivated quadrivalent influenza vaccine (IIV4) in 675 adults ≥ 65 years of age (NCT01218646)...
July 12, 2017: Human Vaccines & Immunotherapeutics
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