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Influenza challenge studies

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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
#1
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/28622854/linear-dna-vaccine-prepared-by-large-scale-pcr-provides-protective-immunity-against-h1n1-influenza-virus-infection-in-mice
#2
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/28622575/protein-nanoparticle-vaccine-based-on-flagellin-carrier-fused-to-influenza-conserved-epitopes-confers-full-protection-against-influenza-a-virus-challenge
#3
Lei Deng, Jong R Kim, Timothy Z Chang, Han Zhang, Teena Mohan, Julie A Champion, Bao-Zhong Wang
Currently marketed influenza vaccines only confer protection against matching influenza virus strains. The influenza A composition of these vaccines needs to be annually updated. Vaccines that target conserved epitopes of influenza viruses would in principle offer broad cross-protection against influenza A viruses. In our study, we investigated the specific immune responses and protective efficacy of protein nanoparticles based on fusion proteins of flagellin carrier linked to conserved influenza epitopes. We designed fusion proteins by replacing the hyperimmunogenic region of flagellin (FliC) with four tandem copies of the ectodomain of matrix protein 2 (f4M2e), H1 HA2 domain (fHApr8) or H3 HA2 domain (fHAaichi)...
June 13, 2017: Virology
https://www.readbyqxmd.com/read/28613150/toll-like-receptor-tlr-21-signalling-mediated-antiviral-response-against-avian-influenza-virus-infection-correlates-with-macrophage-recruitment-and-nitric-oxide-production
#4
Mohamed Sarjoon Abdul-Cader, Hanaa Ahmed-Hassan, Aruna Amarasinghe, Eva Nagy, Shayan Sharif, Mohamed Faizal Abdul-Careem
Cytosine-guanosinedeoxynucleotide (CpG) DNA can be used for the stimulation of the toll-like receptor (TLR)21 signalling pathway in avian species which ultimately leads to up-regulation of gene transcription for pro-inflammatory molecules including nitric oxide and recruitment of innate immune cells. The objective of this study was to determine the antiviral effect of NO, produced in response to in ovo delivery of CpG DNA, against avian influenza virus (AIV) infection. We found that when CpG DNA is delivered at embryo day (ED)18 in ovo and subsequently challenged with H4N6 AIV at ED19 pre-hatch and day 1 post-hatching, CpG DNA reduces H4N6 AIV replication associated with enhanced NO production and macrophage recruitment in lungs...
June 14, 2017: Journal of General Virology
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
#5
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
#6
Jim 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 its 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 are still not understood in detail...
June 7, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28590990/delirium-upon-presentation-to-the-pediatric-emergency-department-a-case-series
#7
Julie A Augenstein, Eileen J Klein, Chani Traube
The following cases describe children who presented to the emergency department (ED) with a constellation of symptoms consistent with delirium. In each case, there was no identified inciting cause (eg, fever, medications) other than the presence of influenza. All children had variable workups, with 2 children undergoing extensive neurologic evaluation and testing. Clinical recognition of delirium in the pediatric acute care setting can be challenging, but heightened awareness by ED and primary care physicians may lead to earlier diagnosis, prevent unwarranted investigations, and decrease hospitalization...
June 6, 2017: Pediatric Emergency Care
https://www.readbyqxmd.com/read/28590242/heterologous-post-infection-immunity-against-egyptian-avian-influenza-virus-aiv-h9n2-modulates-the-course-of-subsequent-infection-by-highly-pathogenic-aiv-h5n1-but-vaccination-immunity-does-not
#8
Mahmoud M Naguib, Christian Grund, Abdel-Satar Arafa, E M Abdelwhab, Martin Beer, Timm C Harder
In Egypt, zoonotic A/goose/Guangdong/1/96 (gs/GD-like) highly pathogenic avian influenza virus (HPAIV) H5N1 of clade 2.2.1.2 is entrenched in poultry populations and has co-circulated with low-pathogenic avian influenza virus H9N2 of the G1 lineage since 2010. Here, the impact of H9N2 infection or vaccination on the course of consecutive infection with a lethal Egyptian HPAIV H5N1 is studied. Three-week-old chickens were infected with H9N2 or vaccinated with inactivated H9N2 or H5N1 antigens and challenged three weeks later by an HPAIV H5N1...
June 5, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28589357/flow-cytometric-method-measuring-b-cell-surface-immunoglobulin-avidity
#9
Davide Angeletti, Gregory M Frank, Jonathan W Yewdell
The affinity of antibodies for their cognate antigens is a critical aspect of humoral immunity. The immune system has gone to great lengths to evolve a mechanism that enables real time increases in antibody affinity during the course of an immune response. This occurs in germinal centers (GC), which form in spleen and lymph nodes following immunization. GC B cell competition for limiting amount of antigen drives the selection of B cells expressing higher affinity Abs. Remarkably little is known about affinity maturation of B cells in immune responses to all but a handful of small model antigens...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28584297/increased-risk-of-influenza-among-vaccinated-adults-who-are-obese
#10
S D Neidich, W D Green, J Rebeles, E A Karlsson, S Schultz-Cherry, T L Noah, S Chakladar, M G Hudgens, S S Weir, M A Beck
BACKGROUND: Influenza infects 5-15% of the global population each year, and obesity has been shown to be an independent risk factor for increased influenza-related complications including hospitalization and death. However, the risk of developing influenza or ILI in a vaccinated obese adult population has not been addressed. OBJECTIVE: This study evaluated whether obesity was associated with increased risk of influenza and influenza-like illness among vaccinated adults...
June 6, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28581455/attenuation-of-rna-viruses-by-redirecting-their-evolution-in-sequence-space
#11
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/28576571/nontoxic-outer-membrane-vesicles-efficiently-increase-the-efficacy-of-an-influenza-vaccine-in-mice-and-ferrets
#12
Sang-Mu Shim, Eun-Jung Song, Daesub Song, Tae-Young Lee, Doo-Jin Kim, Jeong-Hyun Nam, Dae Gwin Jeong, Chong-Kil Lee, Sang-Hyun Kim, Jeong-Ki Kim
In this study, we developed a further-modified outer membrane vesicle (fmOMV) from the ΔmsbB/ΔpagP mutant of Escherichia coli transformed with the plasmid, pLpxF, in order to use it as an adjuvant for pandemic H1N1 (pH1N1) influenza vaccine. We evaluated the efficacy of the pH1N1 influenza vaccine containing the fmOMV in animal models as compared to the commercial adjuvants, alum or AddaVax(TM). The fmOMV-adjuvanted pH1N1 influenza vaccine induced a significant increase in the humoral immunity; however, this effect was less than that of the AddaVax(TM)...
May 30, 2017: Vaccine
https://www.readbyqxmd.com/read/28567036/nasal-iga-provides-protection-against-human-influenza-challenge-in-volunteers-with-low-serum-influenza-antibody-titre
#13
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
#14
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/28554502/protection-of-white-leghorn-chickens-by-u-s-emergency-h5-vaccination-against-clade-2-3-4-4-h5n2-high-pathogenicity-avian-influenza-virus
#15
Kateri Bertran, Charles Balzli, Dong-Hun Lee, David L Suarez, Darrell R Kapczynski, David E Swayne
During December 2014-June 2015, the U.S. experienced a high pathogenicity avian influenza (HPAI) outbreak caused by clade 2.3.4.4 H5Nx Goose/Guangdong lineage viruses with devastating consequences for the poultry industry. Three vaccines, developed based on updating existing registered vaccines or currently licensed technologies, were evaluated for possible use: an inactivated reverse genetics H5N1 vaccine (rgH5N1) and an RNA particle vaccine (RP-H5), both containing the hemagglutinin gene of clade 2.3.4.4 strain, and a recombinant herpesvirus turkey vectored vaccine (rHVT-H5) containing the hemagglutinin gene of clade 2...
May 26, 2017: Vaccine
https://www.readbyqxmd.com/read/28554058/stockpiled-pre-pandemic-h5n1-influenza-virus-vaccines-with-as03-adjuvant-provide-cross-protection-from-h5n2-clade-2-3-4-4-virus-challenge-in-ferrets
#16
Xiangjie Sun, Jessica A Belser, Joanna A Pulit-Penaloza, Hannah M Creager, Zhu Guo, Stacie N Jefferson, Feng Liu, Ian A York, James Stevens, Taronna R Maines, Daniel B Jernigan, Jacqueline M Katz, Min Z Levine, Terrence M Tumpey
Avian influenza viruses, notably H5 subtype viruses, pose a continuous threat to public health due to their pandemic potential. In recent years, influenza virus H5 subtype split vaccines with novel oil-in-water emulsion based adjuvants (e.g. AS03, MF59) have been shown to be safe, immunogenic, and able to induce broad immune responses in clinical trials, providing strong scientific support for vaccine stockpiling. However, whether such vaccines can provide protection from infection with emerging, antigenically distinct clades of H5 viruses has not been adequately addressed...
May 26, 2017: Virology
https://www.readbyqxmd.com/read/28520789/antigen-specific-immunoglobulin-variable-region-sequencing-measures-humoral-immune-response-to-vaccination-in-the-equine-neonate
#17
Rebecca L Tallmadge, Steven C Miller, Stephen A Parry, Maria Julia B Felippe
The value of prophylactic neonatal vaccination is challenged by the interference of passively transferred maternal antibodies and immune competence at birth. Taken our previous studies on equine B cell ontogeny, we hypothesized that the equine neonate generates a diverse immunoglobulin repertoire in response to vaccination, independently of circulating maternal antibodies. In this study, equine neonates were vaccinated with 3 doses of keyhole limpet hemocyanin (KLH) or equine influenza vaccine, and humoral immune responses were assessed using antigen-specific serum antibodies and B cell Ig variable region sequencing...
2017: PloS One
https://www.readbyqxmd.com/read/28518041/stockpiling-ventilators-for-influenza-pandemics
#18
Hsin-Chan Huang, Ozgur M Araz, David P Morton, Gregory P Johnson, Paul Damien, Bruce Clements, Lauren Ancel Meyers
In preparing for influenza pandemics, public health agencies stockpile critical medical resources. Determining appropriate quantities and locations for such resources can be challenging, given the considerable uncertainty in the timing and severity of future pandemics. We introduce a method for optimizing stockpiles of mechanical ventilators, which are critical for treating hospitalized influenza patients in respiratory failure. As a case study, we consider the US state of Texas during mild, moderate, and severe pandemics...
June 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28511853/immunologic-evaluation-of-10-different-adjuvants-for-use-in-vaccines-for-chickens-against-highly-pathogenic-avian-influenza-virus
#19
Nazir Ahmed Lone, Erica Spackman, Darrell Kapczynski
Avian influenza viruses (AIV) are a threat to poultry production worldwide. Vaccination is utilized as a component of control programs for both high pathogenicity (HP) and low pathogenicity (LP) AIV. Over 95% of all AIV vaccine used in poultry are inactivated, adjuvanted products. To identify the best formulations for chickens, vaccines were prepared with beta-propiolactone (BPL) inactivated A/British Columbia/314514-1/2004 H7N3 LP AIV using ten commercially available or experimental adjuvants. Each vaccine formulation was evaluated for immunogenicity in chickens...
May 13, 2017: Vaccine
https://www.readbyqxmd.com/read/28505524/inactivated-influenza-virus-vaccines-the-future-of-tiv-and-qiv
#20
REVIEW
Michael Schotsaert, Adolfo García-Sastre
Influenza viruses continue to be a major public health concern, despite the availability of vaccines. Currently licensed influenza vaccines aim at the induction of antibodies that target hemagglutinin, the major antigenic determinant on the surface of influenza virions that is responsible for attachment of the virus to the host cell that is to be infected. Currently licensed influenza vaccines come as inactivated or live attenuated influenza vaccines and are trivalent or quadrivalent as they contain antigens of two influenza A and one or two influenza B strains that circulate in the human population, respectively...
May 12, 2017: Current Opinion in Virology
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