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https://www.readbyqxmd.com/read/28807912/safety-and-efficacy-of-mhaa4549a-a-broadly-neutralizing-monoclonal-antibody-in-a-human-influenza-a-challenge-model-a-phase-2-randomized-trial
#1
Jacqueline M McBride, Jeremy J Lim, Tracy Burgess, Rong Deng, Michael A Derby, Mauricio Maia, Priscilla Horn, Omer Siddiqui, Daniel Sheinson, Haiyin Chen-Harris, Elizabeth M Newton, Dimitri Fillos, Denise Nazzal, Carrie M Rosenberger, Maikke B Ohlson, Rob Lambkin-Williams, Hosnieh Fathi, Jeffrey M Harris, Jorge A Tavel
BACKGROUND: MHAA4549A, a human monoclonal antibody targeting the hemagglutinin stalk region of influenza A virus (IAV), is being developed as a therapeutic for patients hospitalized with severe IAV infection. Safety and efficacy of MHAA4549A were assessed in a randomized, double-blind, placebo-controlled, dose-ranging study in a human IAV-challenge model. METHODS: One hundred healthy volunteers were inoculated with A/Wisconsin/67/2005 (H3N2) IAV and, 24-36 hours later, administered a single intravenous dose of either placebo, MHAA4549A (400, 1200, or 3600 mg) or a standard oral dose of oseltamivir...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28790324/the-h7n9-influenza-a-virus-infection-results-in-lethal-inflammation-in-the-mammalian-host-via-the-nlrp3-caspase-1-inflammasome
#2
Rongrong Ren, Shuxian Wu, Jialin Cai, Yuqin Yang, Xiaonan Ren, Yanling Feng, Lixiang Chen, Boyin Qin, Chunhua Xu, Hua Yang, Zhigang Song, Di Tian, Yunwen Hu, Xiaohui Zhou, Guangxun Meng
The avian origin influenza A virus (IAV) H7N9 has caused a considerable number of human infections associated with high rates of death since its emergence in 2013. As a vital component of the host innate immune system, the nucleotide-binding domain leucine-rich repeat containing receptor, pyrin domain containing 3 (NLRP3) inflammasome plays a critical role against H1N1 viral infection. However, the function of NLRP3 inflammasome in host immunological responses to the lethal H7N9 virus is still obscure. Here, we demonstrated that mice deficient for NLRP3 inflammasome components, including NLRP3, caspase-1, and Apoptosis-associated speck-like protein containing a CARD (ASC), were less susceptible to H7N9 viral challenge than wild type (WT) controls...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28783091/evolution-of-influenza-a-virus-by-mutation-and-re-assortment
#3
REVIEW
Wenhan Shao, Xinxin Li, Mohsan Ullah Goraya, Song Wang, Ji-Long Chen
Influenza A virus (IAV), a highly infectious respiratory pathogen, has continued to be a significant threat to global public health. To complete their life cycle, influenza viruses have evolved multiple strategies to interact with a host. A large number of studies have revealed that the evolution of influenza A virus is mainly mediated through the mutation of the virus itself and the re-assortment of viral genomes derived from various strains. The evolution of influenza A virus through these mechanisms causes worldwide annual epidemics and occasional pandemics...
August 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28771513/a-modified-vaccinia-ankara-vaccine-vector-expressing-a-mosaic-h5-hemagglutinin-reduces-viral-shedding-in-rhesus-macaques
#4
Nicholas W Florek, Attapon Kamlangdee, James P Mutschler, Brock Kingstad-Bakke, Nancy Schultz-Darken, Karl W Broman, Jorge E Osorio, Thomas C Friedrich
The rapid antigenic evolution of influenza viruses requires frequent vaccine reformulations. Due to the economic burden of continuous vaccine reformulation and the threat of new pandemics, there is intense interest in developing vaccines capable of eliciting broadly cross-reactive immunity to influenza viruses. We recently constructed a "mosaic" hemagglutinin (HA) based on subtype 5 HA (H5) and designed to stimulate cellular and humoral immunity to multiple influenza virus subtypes. Modified vaccinia Ankara (MVA) expressing this H5 mosaic (MVA-H5M) protected mice against multiple homosubtypic H5N1 strains and a heterosubtypic H1N1 virus...
2017: PloS One
https://www.readbyqxmd.com/read/28768855/inactivated-h7-influenza-virus-vaccines-protect-mice-despite-low-levels-of-neutralizing-antibodies
#5
Ram P Kamal, Kristy Blanchfield, Jessica A Belser, Nedzad Music, Wen-Pin Tzeng, Crystal Holiday, Ashley Burroughs, Xiangjie Sun, Taronna R Maines, Min Z Levine, Ian A York
Avian influenza viruses of the H7 hemagglutinin (HA) subtype present a significant public health threat, as evidenced by the ongoing outbreak of human A(H7N9) infections in China. When evaluated by hemagglutinin inhibition (HI) and micro-neutralization (MN) assays, H7 viruses and vaccines induce lower level of neutralizing antibodies (nAb) than do their seasonal counterparts, making it difficult to develop and evaluate pre-pandemic vaccines. We have previously shown that purified recombinant H7 hemagglutinin (HA) appear to be poorly immunogenic in that they induce low levels of HI and MN antibodies...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28737040/potential-of-small-molecule-fungal-metabolites-in-antiviral-chemotherapy
#6
REVIEW
Biswajit G Roy
Various viral diseases, such as acquired immunodeficiency syndrome, influenza, and hepatitis, have emerged as leading causes of human death worldwide. Scientific endeavor since invention of DNA-dependent RNA polymerase of pox virus in 1967 resulted in better understanding of virus replication and development of various novel therapeutic strategies. Despite considerable advancement in every facet of drug discovery process, development of commercially viable, safe, and effective drugs for these viruses still remains a big challenge...
August 2017: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/28723925/immunologic-response-to-vaccine-challenge-in-pregnant-ptpn22-r620w-carriers-and-non-carriers
#7
Shelly H Tien, Juliet N Crabtree, Heather L Gray, Erik J Peterson
OBJECTIVES: Influenza infection is a significant cause of respiratory morbidity among pregnant women. Seasonal influenza vaccination engages innate immune receptors to promote protective immunity. A coding polymorphism (R620W) in PTPN22 imparts elevated risk for human infection and autoimmune disease, predisposes to diminished innate immune responses, and associates with reduced immunization responses. We sought to quantify the effects of PTPN22-R620W on humoral and cell-mediated immune responses to the inactivated influenza vaccine among healthy pregnant women...
2017: PloS One
https://www.readbyqxmd.com/read/28722241/mineralized-state-of-the-avian-influenza-virus-in-the-environment
#8
Hangyu Zhou, Guangchuan Wang, Xiaoyu Wang, Zhiyong Song, Ruikang Tang
Although the circulation of avian influenza in humans is limited, they can be transmitted from Aves to humans, representing a great challenge. Herein, we suggest that influenza viruses from Aves might exist in a mineralized state due to the high calcium concentrations in the avian intestine. Using two typical influenza viruses as examples, we demonstrate these viruses can self-mineralize in simulated avian intestinal fluid, resulting in egg-like virus-mineral structured composites. The mineralized viruses are more robust, with enhanced infectivity and thermostability...
July 18, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28718801/from-variation-of-influenza-viral-proteins-to-vaccine-development
#9
REVIEW
Wandi Zhu, Chao Wang, Bao-Zhong Wang
Recurrent influenza epidemics and occasional pandemics are one of the most important global public health concerns and are major causes of human morbidity and mortality. Influenza viruses can evolve through antigen drift and shift to overcome the barriers of human immunity, leading to host adaption and transmission. Mechanisms underlying this viral evolution are gradually being elucidated. Vaccination is an effective method for the prevention of influenza virus infection. However, the emergence of novel viruses, including the 2009 pandemic influenza A (H1N1), the avian influenza A virus (H7N9), and the highly pathogenic avian influenza A virus (HPAI H5N1), that have infected human populations frequently in recent years reveals the tremendous challenges to the current influenza vaccine strategy...
July 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28702195/molecular-indices-of-viral-disease-development-in-wild-migrating-salmon-%C3%A2
#10
Kristina M Miller, Oliver P Günther, Shaorong Li, Karia H Kaukinen, Tobi J Ming
Infectious diseases can impact the physiological performance of individuals, including their mobility, visual acuity, behavior and tolerance and ability to effectively respond to additional stressors. These physiological effects can influence competitiveness, social hierarchy, habitat usage, migratory behavior and risk to predation, and in some circumstances, viability of populations. While there are multiple means of detecting infectious agents (microscopy, culture, molecular assays), the detection of infectious diseases in wild populations in circumstances where mortality is not observable can be difficult...
2017: Conservation Physiology
https://www.readbyqxmd.com/read/28659900/efficacy-of-live-attenuated-h9n2-influenza-vaccine-candidates-containing-ns1-truncations-against-h9n2-avian-influenza-viruses
#11
Sujuan Chen, Yinbiao Zhu, Da Yang, Yang Yang, Shaohua Shi, Tao Qin, Daxin Peng, Xiufan Liu
H9N2 avian influenza virus is a zoonotic agent with a broad host range that can contribute genetic information to H5 or H7N9 subtype viruses, which are significant threats to both humans and birds. Thus, there is a great need for a vaccine to control H9N2 avian influenza. Three mutant viruses of an H9N2 virus A/chicken/Taixing/10/2010 (rTX-NS1-73, rTX-NS1-100, and rTX-NS1-128) were constructed with different NS1 gene truncations and confirmed by western blot analysis. The genetic stability, pathogenicity, transmissibility, and host immune responses toward these mutants were evaluated...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28639229/pharmacokinetics-of-mhaa4549a-an-anti-influenza-a-monoclonal-antibody-in-healthy-subjects-challenged-with-influenza%C3%A2-a-virus-in-a-phase-iia-randomized-trial
#12
Rong Deng, Ai Ping Lee, Mauricio Maia, Jeremy J Lim, Tracy Burgess, Priscilla Horn, Michael A Derby, Elizabeth Newton, Jorge A Tavel, William D Hanley
BACKGROUND AND OBJECTIVES: MHAA4549A, a human anti-influenza immunoglobulin (Ig) G1 monoclonal antibody, is being developed to treat patients hospitalized for influenza A infection. This study examined the pharmacokinetics (PKs) of MHAA4549A in a phase IIa, randomized, double-blind, dose-ranging trial in healthy volunteers challenged with influenza A virus. METHODS: Serum PK data were collected from 60 subjects in three single-dose groups (400, 1200, or 3600 mg) who received MHAA4549A intravenously 24-36 h after inoculation with the influenza A virus...
June 21, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28606804/a-human-challenge-model-for-respiratory-syncytial-virus-kinetics-the-pharmacological-effect-of-a-novel-fusion-inhibitor-and-the-modeling-of-symptoms-scores
#13
Julia Korell, Bruce Green, John DeVincenzo, Dymphy Huntjens
Respiratory syncytial virus (RSV) causes acute lower respiratory tract infections, and is a major cause of hospital admissions and death in young children. Limited treatments currently exist that can prevent or minimise exacerbation of the disease. The aims of this work were: 1) to develop a population pharmacodynamic model to describe RSV kinetics (RSVK) in nasal lavage, 2) evaluate the impact of an investigational fusion inhibitor, JNJ-53718678, on RSVK, and 3) determine the relationship between RSVK and symptoms scores...
June 9, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28604586/influenza-omics-and-the-host-response-recent-advances-and-future-prospects
#14
REVIEW
Joshua D Powell, Katrina M Waters
Influenza A viruses (IAV) continually evolve and have the capacity to cause global pandemics. Because IAV represents an ongoing threat, identifying novel therapies and host innate immune factors that contribute to IAV pathogenesis is of considerable interest. This review summarizes the relevant literature as it relates to global host responses to influenza infection at both the proteome and transcriptome level. The various-omics infection systems that include but are not limited to ferrets, mice, pigs, and even the controlled infection of humans are reviewed...
June 10, 2017: Pathogens
https://www.readbyqxmd.com/read/28595644/development-of-an-objective-gene-expression-panel-as-an-alternative-to-self-reported-symptom-scores-in-human-influenza-challenge-trials
#15
Julius Muller, Eneida Parizotto, Richard Antrobus, James Francis, Campbell Bunce, Amanda Stranks, Marshall Nichols, Micah McClain, Adrian V S Hill, Adaikalavan Ramasamy, Sarah C Gilbert
BACKGROUND: Influenza challenge trials are important for vaccine efficacy testing. Currently, disease severity is determined by self-reported scores to a list of symptoms which can be highly subjective. A more objective measure would allow for improved data analysis. METHODS: Twenty-one volunteers participated in an influenza challenge trial. We calculated the daily sum of scores (DSS) for a list of 16 influenza symptoms. Whole blood collected at baseline and 24, 48, 72 and 96 h post challenge was profiled on Illumina HT12v4 microarrays...
June 8, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28592526/novel-cross-reactive-monoclonal-antibodies-against-ebolavirus-glycoproteins-show-protection-in-a-murine-challenge-model
#16
James Duehr, Teddy John Wohlbold, Lisa Oestereich, Veronika Chromikova, Fatima Amanat, Madhusudan Rajendran, Sergio Gomez-Medina, Ignacio Mena, Benjamin R tenOever, Adolfo García-Sastre, Christopher F Basler, Cesar Munoz-Fontela, Florian Krammer
Out of an estimated 31,100 cases since their discovery in 1976, ebolaviruses have caused approximately 13,000 deaths. The vast majority (∼11,000) of these occurred during the 2013-2016 West African epidemic. Three out of five species in the genus are known to cause Ebola Virus Disease in humans. Several monoclonal antibodies against the ebolavirus glycoprotein are currently in development as therapeutics. However, there is still a paucity of monoclonal antibodies that can cross-react between the glycoproteins of different ebolavirus species, and the mechanism of these monoclonal antibody therapeutics is still not understood in detail...
August 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28581455/attenuation-of-rna-viruses-by-redirecting-their-evolution-in-sequence-space
#17
Gonzalo Moratorio, Rasmus Henningsson, Cyril Barbezange, Lucia Carrau, Antonio V Bordería, Hervé Blanc, Stephanie Beaucourt, Enzo Z Poirier, Thomas Vallet, Jeremy Boussier, Bryan C Mounce, Magnus Fontes, Marco Vignuzzi
RNA viruses pose serious threats to human health. Their success relies on their capacity to generate genetic variability and, consequently, on their adaptive potential. We describe a strategy to attenuate RNA viruses by altering their evolutionary potential. We rationally altered the genomes of Coxsackie B3 and influenza A viruses to redirect their evolutionary trajectories towards detrimental regions in sequence space. Specifically, viral genomes were engineered to harbour more serine and leucine codons with nonsense mutation targets: codons that could generate Stop mutations after a single nucleotide substitution...
June 5, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28567036/nasal-iga-provides-protection-against-human-influenza-challenge-in-volunteers-with-low-serum-influenza-antibody-titre
#18
Victoria M W Gould, James N Francis, Katie J Anderson, Bertrand Georges, Alethea V Cope, John S Tregoning
In spite of there being a number of vaccines, influenza remains a significant global cause of morbidity and mortality. Understanding more about natural and vaccine induced immune protection against influenza infection would help to develop better vaccines. Virus specific IgG is a known correlate of protection, but other factors may help to reduce viral load or disease severity, for example IgA. In the current study we measured influenza specific responses in a controlled human infection model using influenza A/California/2009 (H1N1) as the challenge agent...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28559489/in-vivo-imaging-of-influenza-virus-infection-in-immunized-mice
#19
Rita Czakó, Leatrice Vogel, Elaine W Lamirande, Kevin W Bock, Ian N Moore, Ali H Ellebedy, Rafi Ahmed, Andrew Mehle, Kanta Subbarao
Immunization is the cornerstone of seasonal influenza control and represents an important component of pandemic preparedness strategies. Using a bioluminescent reporter virus, we demonstrate the application of noninvasive in vivo imaging system (IVIS) technology to evaluate the preclinical efficacy of candidate vaccines and immunotherapy in a mouse model of influenza. Sequential imaging revealed distinct spatiotemporal kinetics of bioluminescence in groups of mice passively or actively immunized by various strategies that accelerated the clearance of the challenge virus at different rates and by distinct mechanisms...
May 30, 2017: MBio
https://www.readbyqxmd.com/read/28536432/nuclear-translocation-of-hif-1%C3%AE-induced-by-influenza-a-h1n1-infection-is-critical-to-the-production-of-proinflammatory-cytokines
#20
Xinkun Guo, Zhaoqin Zhu, Wanju Zhang, Xiaoxiao Meng, Yong Zhu, Peng Han, Xiaohui Zhou, Yunwen Hu, Ruilan Wang
Infection with the influenza A (H1N1) virus is a major challenge for public health because it can cause severe morbidity and even mortality in humans. The over-secretion of inflammatory cytokines (cytokine storm) is considered to be a key contributor to the severe pneumonia caused by H1N1 infection. It has been reported that hypoxia-inducible factor 1-alpha (HIF-1α) is associated with the production of proinflammatory molecules, but whether HIF-1α participates in the acute inflammatory responses against H1N1 infection is still unclear...
May 24, 2017: Emerging Microbes & Infections
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