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https://www.readbyqxmd.com/read/28303960/the-immune-correlates-of-protection-for-an-avian-influenza-h5n1-vaccine-in-the-ferret-model-using-oil-in-water-adjuvants
#1
Sook-San Wong, Susu Duan, Jennifer DeBeauchamp, Mark Zanin, Lisa Kercher, Stephanie Sonnberg, Thomas Fabrizio, Trushar Jeevan, Jeri-Carol Crumpton, Christine Oshansky, Yilun Sun, Li Tang, Paul Thomas, Richard Webby
Because of the pathogenicity and low incidence of avian influenza virus infections in humans, the immune correlates of protection for avian influenza vaccines cannot be determined from clinical studies. Here, we used the ferret model to address this for an avian influenza H5N1 vaccine. Using oil-in-water adjuvants, we generated groups of ferrets with undetectable (geometric mean titer [GMT] < 10), low (GMT = 28.3), or high (GMT > 761.1) hemagglutination-inhibition (HAI) titers to the A/Viet Nam/1203/2004 (H5N1) virus...
March 17, 2017: Scientific Reports
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
#2
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/28285982/evaluation-of-seasonal-influenza-vaccines-for-h1n1pdm09-and-type-b-viruses-based-on-a-replication-incompetent-pb2-ko-virus
#3
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/28282375/a-human-judgment-approach-to-epidemiological-forecasting
#4
David C Farrow, Logan C Brooks, Sangwon Hyun, Ryan J Tibshirani, Donald S Burke, Roni Rosenfeld
Infectious diseases impose considerable burden on society, despite significant advances in technology and medicine over the past century. Advanced warning can be helpful in mitigating and preparing for an impending or ongoing epidemic. Historically, such a capability has lagged for many reasons, including in particular the uncertainty in the current state of the system and in the understanding of the processes that drive epidemic trajectories. Presently we have access to data, models, and computational resources that enable the development of epidemiological forecasting systems...
March 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28277797/strategies-to-induce-broadly-protective-antibody-responses-to-viral-glycoproteins
#5
F Krammer
Currently, several universal/broadly protective influenza virus vaccine candidates are under development. Many of these vaccines are based on strategies to induce protective antibody responses against the surface glycoproteins of antigenically and genetically diverse influenza viruses. These strategies might also be applicable to surface glycoproteins of a broad range of other important viral pathogens. Areas covered: Common strategies include sequential vaccination with divergent antigens, multivalent approaches, vaccination with glycan-modified antigens, vaccination with minimal antigens and vaccination with antigens that have centralized/optimized sequences...
February 23, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28267619/protection-of-human-influenza-vaccines-against-a-reassortant-swine-influenza-virus-of-pandemic-h1n1-origin-using-a-pig-model
#6
Jirapat Arunorat, Nataya Charoenvisal, Yonlayong Woonwong, Roongtham Kedkovid, Supattra Jittimanee, Panchan Sitthicharoenchai, Sawang Kesdangsakonwut, Pariwat Poolperm, Roongroje Thanawongnuwech
Since the pandemic H1N1 emergence in 2009 (pdmH1N1), many reassortant pdmH1N1 viruses emerged and found circulating in the pig population worldwide. Currently, commercial human subunit vaccines are used commonly to prevent the influenza symptom based on the WHO recommendation. In case of current reassortant swine influenza viruses transmitting from pigs to humans, the efficacy of current human influenza vaccines is of interest. In this study, influenza A negative pigs were vaccinated with selected commercial human subunit vaccines and challenged with rH3N2...
February 28, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28262734/continual-antigenic-diversification-in-china-leads-to-global-antigenic-complexity-of-avian-influenza-h5n1-viruses
#7
Yousong Peng, Xiaodan Li, Hongbo Zhou, Aiping Wu, Libo Dong, Ye Zhang, Rongbao Gao, Hong Bo, Lei Yang, Dayan Wang, Xian Lin, Meilin Jin, Yuelong Shu, Taijiao Jiang
The highly pathogenic avian influenza (HPAI) H5N1 virus poses a significant potential threat to human society due to its wide spread and rapid evolution. In this study, we present a comprehensive antigenic map for HPAI H5N1 viruses including 218 newly sequenced isolates from diverse regions of mainland China, by computationally separating almost all HPAI H5N1 viruses into 15 major antigenic clusters (ACs) based on their hemagglutinin sequences. Phylogenetic analysis showed that 12 of these 15 ACs originated in China in a divergent pattern...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28257797/bispecific-t-cell-engaging-antibody-constructs-targeting-a-universally-conserved-part-of-the-viral-m2-ectodomain-cure-and-prevent-influenza-a-virus-infection
#8
Jochen Pendzialek, Kenny Roose, Anouk Smet, Bert Schepens, Peter Kufer, Tobias Raum, Patrick A Baeuerle, Markus Muenz, Xavier Saelens, Walter Fiers
The ectodomain of the influenza A matrix protein 2 (M2e) is highly conserved amongst all influenza virus A subtypes. M2e is present on the surface of influenza A virus-infected cells, and therefore a suitable target for broadly protective therapies. We designed bispecific T cell engaging (BiTE(®)) antibody constructs specific for M2e by genetically fusing a single chain variable fragment (scFv) derived from an M2e-specific murine monoclonal antibody with a CD3ɛ-specific scFv. These so-called FLU BiTE(®) antibody constructs selectively mediate T cell dependent lysis of M2-expressing and influenza A virus infected cells and protect BALB/c mice against challenge with different influenza A virus subtypes...
March 1, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28245096/triple-reassortant-influenza-a-virus-with-h3-of-human-seasonal-origin-na-of-swine-origin-and-internal-a-h1n1-pandemic-2009-genes-is-established-in-danish-pigs
#9
Jesper Schak Schak Krog, Charlotte Kristiane Hjulsager, Michael Albin Larsen, Lars Erik Larsen
The present report describe a triple-reassortant influenza A virus with a HA that resembles H3 of human seasonal influenza from 2004/2005, N2 from influenza A virus already established in swine and the internal gene cassette from A(H1N1)pdm09, has spread in Danish pig herds. The virus has been detected in several Danish pig herds during the last two-three years and may possess a challenge for human as well as animal health.
February 28, 2017: Influenza and Other Respiratory Viruses
https://www.readbyqxmd.com/read/28238698/nasopharyngeal-protein-biomarkers-of-acute-respiratory-virus-infection
#10
Thomas W Burke, Ricardo Henao, Erik Soderblom, Ephraim L Tsalik, J Will Thompson, Micah T McClain, Marshall Nichols, Bradly P Nicholson, Timothy Veldman, Joseph E Lucas, M Arthur Moseley, Ronald B Turner, Robert Lambkin-Williams, Alfred O Hero, Christopher W Woods, Geoffrey S Ginsburg
Infection of respiratory mucosa with viral pathogens triggers complex immunologic events in the affected host. We sought to characterize this response through proteomic analysis of nasopharyngeal lavage in human subjects experimentally challenged with influenza A/H3N2 or human rhinovirus, and to develop targeted assays measuring peptides involved in this host response allowing classification of acute respiratory virus infection. Unbiased proteomic discovery analysis identified 3285 peptides corresponding to 438 unique proteins, and revealed that infection with H3N2 induces significant alterations in protein expression...
February 21, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28230525/inference-and-forecast-of-h7n9-influenza-in-china-2013-to-2015
#11
Ruiyun Li, Yuqi Bai, Alex Heaney, Sasikiran Kandula, Jun Cai, Xuyi Zhao, Bing Xu, Jeffrey Shaman
The recent emergence of A(H7N9) avian influenza poses a significant challenge to public health in China and around the world; however, understanding of the transmission dynamics and progression of influenza A(H7N9) infection in domestic poultry, as well as spillover transmission to humans, remains limited. Here, we develop a mathematical model-Bayesian inference system which combines a simple epidemic model and data assimilation method, and use it in conjunction with data on observed human influenza A(H7N9) cases from 19 February 2013 to 19 September 2015 to estimate key epidemiological parameters and to forecast infection in both poultry and humans...
February 16, 2017: Euro Surveillance: Bulletin Européen sur les Maladies Transmissibles, European Communicable Disease Bulletin
https://www.readbyqxmd.com/read/28228559/targeting-influenza-virus-hemagglutinin-to-xcr1-dendritic-cells-in-the-absence-of-receptor-mediated-endocytosis-enhances-protective-antibody-responses
#12
Arnar Gudjonsson, Anna Lysén, Sreekumar Balan, Vibeke Sundvold-Gjerstad, Catharina Arnold-Schrauf, Lisa Richter, Espen S Bækkevold, Marc Dalod, Bjarne Bogen, Even Fossum
Targeting Ags to conventional dendritic cells can enhance Ag-specific immune responses. Although most studies have focused on the induction of T cell responses, the mechanisms by which targeting improves Ab responses are poorly understood. In this study we present data on the use of human XCL1 (hXCL1) and hXCL2 fusion vaccines in a murine model. We show that the human chemokines bound type 1 conventional dendritic cells (cDC1), and that immunization with influenza virus hemagglutinin fused to hXCL1 or hXCL2 induced full protection against influenza challenge...
February 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28215994/safe-recombinant-outer-membrane-vesicles-that-display-m2e-elicit-heterologous-influenza-protection
#13
Hannah C Watkins, C Garrett Rappazzo, Jaclyn S Higgins, Xiangjie Sun, Nicole Brock, Annie Chau, Aditya Misra, Joseph P B Cannizzo, Michael R King, Taronna R Maines, Cynthia A Leifer, Gary R Whittaker, Matthew P DeLisa, David Putnam
Recombinant, Escherichia coli-derived outer membrane vesicles (rOMVs), which display heterologous protein subunits, have potential as a vaccine adjuvant platform. One drawback to rOMVs is their lipopolysaccharide (LPS) content, limiting their translatability to the clinic due to potential adverse effects. Here, we explore a unique rOMV construct with structurally remodeled lipids containing only the lipid IVa portion of LPS, which does not stimulate human TLR4. The rOMVs are derived from a genetically engineered B strain of E...
February 16, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28213653/perceived-risk-of-avian-influenza-and-urbanization-in-northern-vietnam
#14
Melissa L Finucane, Nghiem Tuyen, Sumeet Saksena, James H Spencer, Jefferson M Fox, Nguyen Lam, Trinh Dinh Thau, Tran Duc Vien, Nancy Davis Lewis
Highly pathogenic avian influenza (HPAI) is an important public health concern because of potential for widespread morbidity and mortality in humans and poultry and associated devastating economic losses. We examined how perceptions of the risk of HPAI in poultry vary across communes/wards in the north of Vietnam at different levels of urbanization (rural, peri-urban, urban). Analyses of questionnaire responses from 1081 poultry raisers suggested that the perceived risk of HPAI in poultry was highest in peri-urban and rural settings...
February 17, 2017: EcoHealth
https://www.readbyqxmd.com/read/28170438/the-effective-rate-of-influenza-reassortment-is-limited-during-human-infection
#15
Ashley Sobel Leonard, Micah T McClain, Gavin J D Smith, David E Wentworth, Rebecca A Halpin, Xudong Lin, Amy Ransier, Timothy B Stockwell, Suman R Das, Anthony S Gilbert, Rob Lambkin-Williams, Geoffrey S Ginsburg, Christopher W Woods, Katia Koelle, Christopher J R Illingworth
We characterise the evolutionary dynamics of influenza infection described by viral sequence data collected from two challenge studies conducted in human hosts. Viral sequence data were collected at regular intervals from infected hosts. Changes in the sequence data observed across time show that the within-host evolution of the virus was driven by the reversion of variants acquired during previous passaging of the virus. Treatment of some patients with oseltamivir on the first day of infection did not lead to the emergence of drug resistance variants in patients...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28143596/a-scalable-algorithm-for-structure-identification-of-complex-gene-regulatory-network-from-temporal-expression-data
#16
Shupeng Gui, Andrew P Rice, Rui Chen, Liang Wu, Ji Liu, Hongyu Miao
BACKGROUND: Gene regulatory interactions are of fundamental importance to various biological functions and processes. However, only a few previous computational studies have claimed success in revealing genome-wide regulatory landscapes from temporal gene expression data, especially for complex eukaryotes like human. Moreover, recent work suggests that these methods still suffer from the curse of dimensionality if a network size increases to 100 or higher. RESULTS: Here we present a novel scalable algorithm for identifying genome-wide gene regulatory network (GRN) structures, and we have verified the algorithm performances by extensive simulation studies based on the DREAM challenge benchmark data...
January 31, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28109707/potential-risk-of-repeated-nasal-vaccination-that-induces-allergic-reaction-with-mucosal-ige-and-airway-eosinophilic-infiltration-in-cynomolgus-macaques-infected-with-h5n1-highly-pathogenic-avian-influenza-virus
#17
Misako Nakayama, Yasushi Itoh, Shintaro Shichinohe, Rumi Nakabayashi, Hirohito Ishigaki, Yoshihiro Sakoda, Quynh Mai Le, Yoshihiro Kawaoka, Hiroshi Kida, Kazumasa Ogasawara
The efficacy and detrimental effect of mucosal vaccination with an inactivated influenza vaccine were examined in a macaque model by intranasal administration with small amounts of inactivated whole virus particles and challenge by a human-derived H5N1 highly pathogenic avian influenza virus infection. Repeated nasal inoculation with the whole particle vaccine of an inactivated virus, A/duck/Hokkaido/Vac-3/2007 (H5N1) (Vac-3), induced antigen-specific IgA and IgG antibody production in nasal swabs and plasma...
January 18, 2017: Vaccine
https://www.readbyqxmd.com/read/28102191/a-broadly-protective-therapeutic-antibody-against-influenza-b-virus-with-two-mechanisms-of-action
#18
Ning Chai, Lee R Swem, Summer Park, Gerald Nakamura, Nancy Chiang, Alberto Estevez, Rina Fong, Lynn Kamen, Elviza Kho, Mike Reichelt, Zhonghua Lin, Henry Chiu, Elizabeth Skippington, Zora Modrusan, Jeremy Stinson, Min Xu, Patrick Lupardus, Claudio Ciferri, Man-Wah Tan
Influenza B virus (IBV) causes annual influenza epidemics around the world. Here we use an in vivo plasmablast enrichment technique to isolate a human monoclonal antibody, 46B8 that neutralizes all IBVs tested in vitro and protects mice against lethal challenge of all IBVs tested when administered 72 h post infection. 46B8 demonstrates a superior therapeutic benefit over Tamiflu and has an additive antiviral effect in combination with Tamiflu. 46B8 binds to a conserved epitope in the vestigial esterase domain of hemagglutinin (HA) and blocks HA-mediated membrane fusion...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28096374/phylogenetic-analysis-of-the-human-antibody-repertoire-reveals-quantitative-signatures-of-immune-senescence-and-aging
#19
Charles F A de Bourcy, Cesar J Lopez Angel, Christopher Vollmers, Cornelia L Dekker, Mark M Davis, Stephen R Quake
The elderly have reduced humoral immunity, as manifested by increased susceptibility to infections and impaired vaccine responses. To investigate the effects of aging on B-cell receptor (BCR) repertoire evolution during an immunological challenge, we used a phylogenetic distance metric to analyze Ig heavy-chain transcript sequences in both young and elderly individuals before and after influenza vaccination. We determined that BCR repertoires become increasingly specialized over a span of decades, but less plastic...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28079473/protective-immunity-against-influenza-in-hla-a2-transgenic-mice-by-modified-vaccinia-virus-ankara-vectored-vaccines-containing-internal-influenza-proteins
#20
Giuseppina Di Mario, Ester Sciaraffia, Marzia Facchini, Francesco Gubinelli, Elisa Soprana, Maddalena Panigada, Valentina Bernasconi, Bruno Garulli, Antonio Siccardi, Isabella Donatelli, Maria R Castrucci
BACKGROUND: The emergence of novel strains of influenza A viruses with hemagglutinins (HAs) that are antigenically distinct from those circulating in humans, and thus have pandemic potential, pose concerns and call for the development of more broadly protective influenza vaccines. In the present study, modified vaccinia virus Ankara (MVA) encoding internal influenza antigens were evaluated for their immunogenicity and ability to protect HLA-A2.1 transgenic (AAD) mice from infection with influenza viruses...
March 2017: Pathogens and Global Health
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