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Influenza hemagglutinin

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https://www.readbyqxmd.com/read/28646236/rapamycin-adjuvant-and-exacerbation-of-severe-influenza-in-an-experimental-mouse-model
#1
Ching-Tai Huang, Chen-Yiu Hung, Tse-Ching Chen, Chun-Yen Lin, Yung-Chang Lin, Chia-Shiang Chang, Yueh-Chia He, Yu-Lin Huang, Avijit Dutta
Influenza virus infection often causes severe disease and acute respiratory distress syndrome. It is a common belief that overwhelming immune response contributes to the severe illness. Physicians and researchers have put forth immune modulation as salvage therapy for better recovery. However, empiric corticosteroid failed in both humans and animal models. Reported success with Rapamycin in humans prompted a comprehensive animal study and mechanistic dissection. Here we report the effect of Rapamycin alone or in combination with Oseltamivir for severe influenza in BALB/c mice...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28640898/competition-between-influenza-a-virus-subtypes-through-heterosubtypic-immunity-modulates-re-infection-and-antibody-dynamics-in-the-mallard-duck
#2
Neus Latorre-Margalef, Justin D Brown, Alinde Fojtik, Rebecca L Poulson, Deborah Carter, Monique Franca, David E Stallknecht
Our overall hypothesis is that host population immunity directed at multiple antigens will influence the prevalence, diversity and evolution of influenza A virus (IAV) in avian populations where the vast subtype diversity is maintained. To investigate how initial infection influences the outcome of later infections with homologous or heterologous IAV subtypes and how viruses interact through host immune responses, we carried out experimental infections in mallard ducks (Anas platyrhynchos). Mallards were pre-challenged with an H3N8 low-pathogenic IAV and were divided into six groups...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28640212/synthesis-and-in-vitro-anti-influenza-virus-evaluation-of-novel-sialic-acid-c-5-and-c-9-pentacyclic-triterpene-derivatives
#3
Xu Han, Long-Long Si, Yong-Ying Shi, Zi-Bo Fan, Shou-Xin Wang, Zhen-Yu Tian, Man Li, Jia-Qi Sun, Ping-Xuan Jiao, Fu-Xiang Ran, Yong-Min Zhang, De-Min Zhou, Su-Long Xiao
The emergence of drug resistant variants of the influenza virus has led to a great need to identify novel and effective antiviral agents. In our previous study, a series of sialic acid (C-2 and C-4)-pentacyclic triterpene conjugates have been synthesized, and a five-fold more potent antiviral activity was observed when sialic acid was conjugated with pentacyclic triterpene via C-4 than C-2. It was here that we further reported the synthesis and anti-influenza activity of novel sialic acid (C-5 and C-9)-pentacyclic triterpene conjugates...
June 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28637337/matrix-completion-with-side-information-and-its-applications-in-predicting-the-antigenicity-of-influenza-viruses
#4
Li Huang, Xianhong Li, Pengfei Guo, Yuhua Yao, Bo Liao, Weiwei Zhang, Fayou Wang, Jiasheng Yang, Yulong Zhao, Hailiang Sun, Pingan He, Jialiang Yang
Motivation: Low-rank matrix completion has been demonstrated to be powerful in predicting antigenic distances among influenza viruses and vaccines from partially revealed hemagglutination inhibition (HI) table. Meanwhile, influenza hemagglutinin (HA) protein sequences are also effective in inferring antigenic distances. Thus, it is natural to integrate HA protein sequence information into low-rank matrix completion model to help infer influenza antigenicity, which is critical to influenza vaccine development...
June 16, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28636855/efficacy-of-recombinant-influenza-vaccine-in-adults-50-years-of-age-or-older
#5
Lisa M Dunkle, Ruvim Izikson, Peter Patriarca, Karen L Goldenthal, Derek Muse, Janice Callahan, Manon M J Cox
BACKGROUND: Improved influenza vaccines are needed to control seasonal epidemics. This trial compared the protective efficacy in older adults of a quadrivalent, recombinant influenza vaccine (RIV4) with a standard-dose, egg-grown, quadrivalent, inactivated influenza vaccine (IIV4) during the A/H3N2-predominant 2014-2015 influenza season, when antigenic mismatch between circulating and vaccine influenza strains resulted in the reduced effectiveness of many licensed vaccines. METHODS: We conducted a randomized, double-blind, multicenter trial of RIV4 (45 μg of recombinant hemagglutinin [HA] per strain, 180 μg of protein per dose) versus standard-dose IIV4 (15 μg of HA per strain, 60 μg of protein per dose) to compare the relative vaccine efficacy against reverse-transcriptase polymerase-chain-reaction (RT-PCR)-confirmed, protocol-defined, influenza-like illness caused by any influenza strain starting 14 days or more after vaccination in adults who were 50 years of age or older...
June 22, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28633988/a-cross-clade-h5n1-influenza-a-virus-neutralizing-monoclonal-antibody-binds-to-a-novel-epitope-within-the-vestigial-esterase-domain-of-hemagglutinin
#6
Subha Sankar Paul, Chee-Keng Mok, Tze-Minn Mak, Oi-Wing Ng, James Odame Aboagye, Teddy John Wohlbold, Florian Krammer, Yee-Joo Tan
The sporadic outbreaks of highly pathogenic H5N1 avian influenza virus have raised public health concerns. Monoclonal antibodies (MAbs) against hemagglutinin (HA) have been increasingly used successfully for therapeutic purposes. Previously, MAb 9F4, generated against clade 1 H5N1 HA, was observed to have cross-clade neutralizing efficacy and inhibited viral entry by preventing the pH-mediated conformational change of HA. Furthermore, mouse-human chimeric MAb 9F4 was found to retain high degrees of neutralizing activity...
June 17, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28630402/exploration-of-binding-and-inhibition-mechanism-of-a-small-molecule-inhibitor-of-influenza-virus-h1n1-hemagglutinin-by-molecular-dynamics-simulation
#7
Shanshan Guan, Tianao Wang, Ziyu Kuai, Mengdan Qian, Xiaopian Tian, Xiuqi Zhang, Yongjiao Yu, Song Wang, Hao Zhang, Hao Li, Wei Kong, Yaming Shan
Influenza viruses are a major public health threat worldwide. The influenza hemagglutinin (HA) plays an essential role in the virus life cycle. Due to the high conservation of the HA stem region, it has become an especially attractive target for inhibitors for therapeutics. In this study, molecular simulation was applied to study the mechanism of a small molecule inhibitor (MBX2329) of influenza HA. Behaviors of the small molecule under neutral and acidic conditions were investigated, and an interesting dynamic binding mechanism was found...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28624584/antibody-dependent-nk-cell-degranulation-as-a-marker-for-assessing-antibody-dependent-cytotoxicity-against-pandemic-2009-influenza-a-h1n1-infection-in-human-plasma-and-influenza-vaccinated-transchromosomic-bovine-intravenous-immunoglobulin-therapy
#8
Brian J Morrison, Jessica A Roman, Thomas C Luke, Nishith Nagabhushana, Kanakatte Raviprakash, Maya Williams, Peifang Sun
This study describes an antibody-dependent NK cell degranulation assay, as a biomarker to assess antibody-dependent cellular cytotoxicity (ADCC) response in influenza plasma and for antibody therapies against influenza infection. The concentration of neutralizing antibodies (NAbs) against the hemagglutinin receptor of influenza viruses is a current determinant in protection against infection, particularly following receipt of the seasonal influenza vaccine. However, this is a limited assessment of protection, because: (i) NAb titers that incur full protection vary; and (ii) NAb titers do not account for the entire breadth of antibody responses against viral infection...
June 15, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28622854/linear-dna-vaccine-prepared-by-large-scale-pcr-provides-protective-immunity-against-h1n1-influenza-virus-infection-in-mice
#9
Fei Wang, Quanjiao Chen, Shuntang Li, Chenyao Zhang, Shanshan Li, Min Liu, Kun Mei, Chunhua Li, Lixin Ma, Xiaolan Yu
Linear DNA vaccines provide effective vaccination. However, their application is limited by high cost and small scale of the conventional polymerase chain reaction (PCR) generally used to obtain sufficient amounts of DNA effective against epidemic diseases. In this study, a two-step, large-scale PCR was established using a low-cost DNA polymerase, RKOD, expressed in Pichia pastoris. Two linear DNA vaccines encoding influenza H1N1 hemagglutinin (HA) 1, LEC-HA, and PTO-LEC-HA (with phosphorothioate-modified primers), were produced by the two-step PCR...
June 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28622853/preexisting-salmonella-specific-immunity-interferes-with-the-subsequent-development-of-immune-responses-against-the-salmonella-strains-delivering-h9n2-hemagglutinin
#10
Irshad Ahmed Hajam, John Hwa Lee
Recombinant Salmonella strains expressing foreign heterologous antigens have been extensively studied as promising live vaccine delivery vehicles. In this study, we constructed attenuated smooth (S-HA) and rough (R-HA) Salmonella strains expressing hemagglutinin (HA) of H9N2, a low pathogenic avian influenza A virus. We then investigated the HA-specific immune responses following oral immunization with either S-HA or R-HA strain in chicken model. We further examined the effects of the preexisting anti-Salmonella immunity on the subsequent elicitation of the HA and the Salmonella ompA specific immune responses...
June 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28620653/successive-annual-influenza-vaccination-induces-a-recurrent-oligoclonotypic-memory-response-in-circulating-t-follicular-helper-cells
#11
Ramin Sedaghat Herati, Alexander Muselman, Laura Vella, Bertram Bengsch, Kaela Parkhouse, Daniel Del Alcazar, Jonathan Kotzin, Susan A Doyle, Pablo Tebas, Scott E Hensley, Laura F Su, Kenneth E Schmader, E John Wherry
T follicular helper (Tfh) CD4 cells are crucial providers of B cell help during adaptive immune responses. A circulating population of CD4 T cells, termed cTfh, have similarity to lymphoid Tfh, can provide B cell help, and responded to influenza vaccination. However, it is unclear whether human vaccination-induced cTfh respond in an antigen-specific manner and whether they form long-lasting memory. Here, we identified a cTfh population that expressed multiple T cell activation markers and could be readily identified by coexpression of ICOS and CD38...
February 2017: Science Immunology
https://www.readbyqxmd.com/read/28619173/vaccine-immune-pressure-influences-viral-population-complexity-of-avian-influenza-virus-during-infection
#12
Adelaide Milani, Alice Fusaro, Francesco Bonfante, Gianpiero Zamperin, Annalisa Salviato, Marzia Mancin, Eleonora Mastrorilli, Joseph Hughes, Hussein A Hussein, Magdi Hassan, Egbert Mundt, Calogero Terregino, Giovanni Cattoli, Isabella Monne
Vaccines are useful tools to control influenza A virus infection in poultry, but they need to be periodically reformulated to guarantee appropriate protection from infection and to limit viral replication and circulation, which could favour the emergence of new variants. In this study, a deep sequencing approach was used to characterize and follow the evolution of the hemagglutinin of the H5N1 highly pathogenic avian influenza viral population in infected animals vaccinated with two vaccines conferring different protection levels...
May 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28619136/coimmunization-with-recombinant-epitope-expressing-baculovirus-enhances-protective-effects-of-inactivated-h5n1-vaccine-against-heterologous-virus
#13
Zhen Zhang, Jiao Zhang, Jie Zhang, Qi Li, Peisi Miao, Jie Liu, Shijie Li, Jianni Huang, Ming Liao, Huiying Fan
H5N1, a highly pathogenic avian influenza virus (HPAIV), poses a significant threat to poultry and human health. However, currently available inactivated influenza vaccines are less efficacious against viruses that display antigenic drift. In this study, we constructed a recombinant baculovirus (BV-HMNN) expressing four conserved antigen epitopes: H5N1 hemagglutinin stem area amino acids 76-130 (HA2 76-130); three tandem repeats from the ectodomain of the conserved influenza matrix protein M2 (3M2e); nucleoprotein amino acids 55-69 (NP55-69); and nucleoprotein amino acids 380-393 (NP380-393)...
May 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28618270/diversity-of-functionally-permissive-sequences-in-the-receptor-binding-site-of-influenza-hemagglutinin
#14
Nicholas C Wu, Jia Xie, Tianqing Zheng, Corwin M Nycholat, Geramie Grande, James C Paulson, Richard A Lerner, Ian A Wilson
Influenza A virus hemagglutinin (HA) initiates viral entry by engaging host receptor sialylated glycans via its receptor-binding site (RBS). The amino acid sequence of the RBS naturally varies across avian and human influenza virus subtypes and is also evolvable. However, functional sequence diversity in the RBS has not been fully explored. Here, we performed a large-scale mutational analysis of the RBS of A/WSN/33 (H1N1) and A/Hong Kong/1/1968 (H3N2) HAs. Many replication-competent mutants not yet observed in nature were identified, including some that could escape from an RBS-targeted broadly neutralizing antibody...
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28617868/three-mutations-switch-h7n9-influenza-to-human-type-receptor-specificity
#15
Robert P de Vries, Wenjie Peng, Oliver C Grant, Andrew J Thompson, Xueyong Zhu, Kim M Bouwman, Alba T Torrents de la Pena, Marielle J van Breemen, Iresha N Ambepitiya Wickramasinghe, Cornelis A M de Haan, Wenli Yu, Ryan McBride, Rogier W Sanders, Robert J Woods, Monique H Verheije, Ian A Wilson, James C Paulson
The avian H7N9 influenza outbreak in 2013 resulted from an unprecedented incidence of influenza transmission to humans from infected poultry. The majority of human H7N9 isolates contained a hemagglutinin (HA) mutation (Q226L) that has previously been associated with a switch in receptor specificity from avian-type (NeuAcα2-3Gal) to human-type (NeuAcα2-6Gal), as documented for the avian progenitors of the 1957 (H2N2) and 1968 (H3N2) human influenza pandemic viruses. While this raised concern that the H7N9 virus was adapting to humans, the mutation was not sufficient to switch the receptor specificity of H7N9, and has not resulted in sustained transmission in humans...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28615200/kallikrein-related-peptidase-5-contributes-to-h3n2-influenza-virus-infection-in-human-lungs
#16
Melia Magnen, Fabien Gueugnon, Antoine Guillon, Thomas Baranek, Virginie C Thibault, Agnès Petit-Courty, Simon J de Veer, Jonathan Harris, Alison A Humbles, Mustapha Si-Tahar, Yves Courty
The HA (hemagglutinin) of influenza virus must be activated by proteolysis before the virus can become infectious. Previous studies have indicated that HA cleavage is driven by membrane-bound or extracellular serine proteases in the respiratory tract. However, there is still uncertainty as to which proteases are critical for activating the HA of seasonal influenza A viruses (IAV) in humans. This study focuses on human KLK1 and KLK5, two of the 15 serine proteases known as the kallikrein-related peptidases (KLK)...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28613978/increased-humoral-immunity-by-dna-vaccination-using-an-%C3%AE-tocopherol-based-adjuvant
#17
Ingrid Karlsson, Marie Borggren, Jens Nielsen, Dennis Christensen, Jim Williams, Anders Fomsgaard
DNA vaccines induce broad immunity, which involves both humoral and strong cellular immunity, and can be rapidly designed for novel or evolving pathogens such as influenza. However, the humoral immunogenicity in humans and higher animals has been suboptimal compared with that of traditional vaccine approaches. We tested whether the emulsion-based and α-tocopherol containing adjuvant Diluvac Forte® has the ability to enhance the immunogenicity of a naked DNA vaccine (i.e., plasmid DNA). As a model vaccine, we used plasmids encoding both a surface-exposed viral glycoprotein (hemagglutinin) and an internal non-glycosylated nucleoprotein in the Th1/Th2 balanced CB6F1 mouse model...
June 14, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28612840/toll-like-receptor-3-in-nasal-cd103-dendritic-cells-is-involved-in-immunoglobulin-a-production
#18
H Takaki, S Kure, H Oshiumi, Y Sakoda, T Suzuki, A Ainai, H Hasegawa, M Matsumoto, T Seya
Intranasal inoculation with influenza hemagglutinin subunit with polyinosine-polycytidylic (polyI:C), a synthetic analog for double-stranded RNA, enhances production of vaccine-specific immunoglobulin (Ig) A, which is superior to IgG in prophylactic immunity. The mechanism whereby polyI:C skews to IgA production in the nasal-associated lymph tissue (NALT) was investigated in mouse models. Nasally instilled polyI:C was endocytosed into CD103(+) dendritic cells (DCs) and induced T-cell activation, including interferon (IFN)-γ production...
June 14, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28612603/sortase-mediated-ligation-as-a-modular-approach-for-the-covalent-attachment-of-proteins-to-the-exterior-of-the-bacteriophage-p22-virus-like-particle
#19
Dustin P Patterson, Benjamin Schwarz, John Avera, Brian Western, Matthew Hicks, Paul Krugler, Matthew Terra, Masaki Uchida, Kimberly McCoy, Trevor Douglas
Virus-like particles are unique platforms well suited for the construction of nanomaterials with broad range applications. The research presented here describes the development of a modular approach for the covalent attachment of protein domains to the exterior of the versatile bacteriophage P22 virus-like particle (VLP) via a sortase-mediated ligation strategy. The bacteriophage P22 coat protein was genetically engineered to incorporate an LPETG amino acid sequence on the C-terminus, providing the peptide recognition sequence utilized by the sortase enzyme to catalyze peptide bond formation between the LPETG-tagged protein and a protein containing a poly-glycine sequence on the N-terminus...
June 14, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28612264/application-of-recombinant-hemagglutinin-proteins-as-alternative-antigen-standards-for-pandemic-influenza-vaccines
#20
Yejin Choi, Seong Yi Kwon, Ho Jung Oh, Sunbo Shim, Seokkee Chang, Hye Joo Chung, Do Keun Kim, Younsang Park, Younghee Lee
OBJECTIVES: The single radial immunodiffusion (SRID) assay, used to quantify hemagglutinin (HA) in influenza vaccines, requires reference reagents; however, because centralized production of reference reagents may slow the emergency deployment of vaccines, alternatives are needed. RESULTS: We investigated the production of HA proteins using recombinant DNA technology, rather than a traditional egg-based production process. The HA proteins were then used in an SRID assay as a reference antigen...
June 13, 2017: Biotechnology Letters
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