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Influenza challenge studies

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https://www.readbyqxmd.com/read/28828973/be-aware-of-immunogenic-but-not-protective-antigens-the-actinobacillus-pleuropneumoniae-pala-as-an-example
#1
Caihong Liu, Yurou Cao, Jihong Yang, Haobin Zhao, Kashif Rafiq Zahid, Jin Zhao, Chao Qi, Jinlin Liu
Identification of immunogenic antigens is an important step for the vaccine improvement of infectious diseases. Previous studies indicated that Actinobacillus pleuropneumoniae PalA is homologous to a Haemophilus influenzae protective antigen Hi-PAL (P6) protein. However, PalA protein adversely affects the Apx toxin-based subunit vaccine. In this study, we confirmed that recombinant PalA is immunogenic in animals. Mice immunized with bacterin and PalA (BacPal) showed significantly less antibodies against Apx toxins, relative to that of animals immunized with bacterin alone (Bac) before challenge...
August 22, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28811215/molecular-mechanisms-underlying-protection-against-h9n2-influenza-virus-challenge-in-mice-by-recombinant-lactobacillus-plantarum-with-surface-displayed-ha2-ltb
#2
Yanlong Jiang, Guilian Yang, Qi Wang, Zhannan Wang, Wentao Yang, Wei Gu, Chunwei Shi, Jianzhong Wang, Haibin Huang, Chunfeng Wang
It has been considered that the Avian influenza virus (AIV) causes severe threats to poultry industry. In this study, we constructed a series of recombinant Lactobacillus plantarum (L. plantarum) with surface displayed hemagglutinin subunit 2 (HA2) alone or together with heat-labile toxin B subunit (LTB) from enterotoxigenic Escherichia coli. Balb/c mice were used as model to evaluate the protective effects of recombinant L. plantarum strains against H9N2 subtype challenge. The results showed that the presence of LTB significantly increased the percentages of CD3(+)CD4(+)IL-4(+), CD3(+)CD4(+)IFN-γ(+) and CD3(+)CD4(+)IL-17(+) T cells, as well as CD3(+)CD8(+)IFN-γ(+) T cells in spleen and MLNs determined by Fluorescence-Activated Cell Sorting assay...
August 12, 2017: Journal of Biotechnology
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
#3
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/28792205/solid-phase-chemical-modification-for-sialic-acid-linkage-analysis-application-to-glycoproteins-of-host-cells-used-in-influenza-virus-propagation
#4
Shuang Yang, Ewa Jankowska, Martina Kosikova, Hang Xie, John Cipollo
Differentiation between the sialyl linkages is often critical to understanding biological consequence. Here we present a facile method for determining these linkages in glycans. Analysis of sialic acids is challenging due to their labile nature during sample preparation and ionization. Derivatization is often required via chemical reaction. Amidation derivatizes all sialic acids regardless of linkage, while esterification enables differentiation between α2,3-linked and α2,6-linked sialic acids. Reactions have been primarily performed on free glycans in solution but have been recently adapted to solid-phase providing unique advantages such as simplified sample preparation, improved yield, and high throughput applications...
August 21, 2017: Analytical Chemistry
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
#5
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
#6
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/28780285/urgent-challenges-in-implementing-live-attenuated-influenza-vaccine
#7
REVIEW
Anika Singanayagam, Maria Zambon, Ajit Lalvani, Wendy Barclay
Conflicting reports have emerged about the effectiveness of the live attenuated influenza vaccine. The live attenuated influenza vaccine appears to protect particularly poorly against currently circulating H1N1 viruses that are derived from the 2009 pandemic H1N1 viruses. During the 2015-16 influenza season, when pandemic H1N1 was the predominant virus, studies from the USA reported a complete lack of effectiveness of the live vaccine in children. This finding led to a crucial decision in the USA to recommend that the live vaccine not be used in 2016-17 and to switch to the inactivated influenza vaccine...
August 2, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28780119/vaccine-efficacy-against-indonesian-highly-pathogenic-avian-influenza-h5n1-systematic-review-and-meta-analysis
#8
REVIEW
Juan P Villanueva-Cabezas, Mauricio J C Coppo, Peter A Durr, Jodie McVernon
Indonesia has implemented multiple strategies to control Highly Pathogenic Avian Influenza H5N1 (HPAI/H5N1), including the licensure and use of multiple vaccine formulations. The continuous drift of Indonesian HPAI/H5N1 viruses and emergence of a new clade in 2012 that became dominant in 2016, demands the assessment of commercial vaccine formulations against Indonesian field viruses. Seven databases were explored to identify relevant literature reporting performance of commercial vaccines against Indonesian HPAI/H5N1 viruses...
August 2, 2017: Vaccine
https://www.readbyqxmd.com/read/28775299/construction-and-evaluation-of-two-computational-models-for-predicting-the-incidence-of-influenza-in-nagasaki-prefecture-japan
#9
Fei He, Zhi-Jian Hu, Wen-Chang Zhang, Lin Cai, Guo-Xi Cai, Kiyoshi Aoyagi
It remains challenging to forecast local, seasonal outbreaks of influenza. The goal of this study was to construct a computational model for predicting influenza incidence. We built two computational models including an Autoregressive Distributed Lag (ARDL) model and a hybrid model integrating ARDL with a Generalized Regression Neural Network (GRNN), to assess meteorological factors associated with temporal trends in influenza incidence. The modelling and forecasting performance of these two models were compared using observations collected between 2006 and 2015 in Nagasaki Prefecture, Japan...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28768855/inactivated-h7-influenza-virus-vaccines-protect-mice-despite-low-levels-of-neutralizing-antibodies
#10
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/28761583/challenges-of-empirical-antibiotic-therapy-for-community-acquired-pneumonia-in-children
#11
REVIEW
Charlene M C Rodrigues
BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality globally, responsible for more than 14% of deaths in children younger than 5 years of age. Due to difficulties with pathogen identification and diagnostics of CAP in children, targeted antimicrobial therapy is not possible, hence the widespread use of empirical antibiotics, in particular penicillins, cephalosporin, and macrolides. OBJECTIVES: This review aimed to address medical, societal, and political issues associated with the widespread use of empirical antibiotics for CAP in the United Kingdom, India, and Nigeria...
2017: Current Therapeutic Research, Clinical and Experimental
https://www.readbyqxmd.com/read/28756116/selection-of-antigenic-variants-of-an-h5n1-highly-pathogenic-avian-influenza-virus-in-vaccinated-chickens
#12
Lam Thanh Nguyen, Tatsuya Nishi, Shintaro Shichinohe, Duc-Huy Chu, Takahiro Hiono, Keita Matsuno, Masatoshi Okamatsu, Hiroshi Kida, Yoshihiro Sakoda
Vaccination-primed immunity in poultry has been suggested for selection of antigenically drifted highly pathogenic avian influenza viruses (HPAIVs). In this study, we performed two consecutive passage studies of an H5N1 HPAIV in vaccinated chickens, namely, study-I and study-II, to select antigenic variants under immune pressure from the vaccination. In study-I, nine consecutive passages of a wild-type H5N1 HPAIV were carried out in chickens vaccinated with the homologous challenge strain. Antigenically drifted variants with mutations at position 179 in the hemagglutinin (HA) were selected after three passages...
July 27, 2017: Virology
https://www.readbyqxmd.com/read/28754303/type-i-ifn-and-not-tnf-is-essential-for-cyclic-di-nucleotide-elicited-ctl-by-a-cytosolic-cross-presentation-pathway
#13
Darío Lirussi, Thomas Ebensen, Kai Schulze, Stephanie Trittel, Veronica Duran, Ines Liebich, Ulrich Kalinke, Carlos A Guzmán
Cyclic di-nucleotides (CDN) are potent stimulators of innate and adaptive immune responses. Cyclic di-AMP (CDA) is a promising adjuvant that generates humoral and cellular immunity. The strong STING-dependent stimulation of type I IFN represents a key feature of CDA. However, recent studies suggested that this is dispensable for adjuvanticity. Here we demonstrate that stimulation of IFN-γ-secreting CD8(+) cytotoxic T lymphocytes (CTL) is significantly decreased after vaccination in the absence of type I IFN signaling...
August 2017: EBioMedicine
https://www.readbyqxmd.com/read/28752641/influenza-virus-like-particles-harboring-h9n2-ha-and-na-proteins-induce-a-protective-immune-response-in-chicken
#14
Xin Li, Houbin Ju, Jian Liu, Dequan Yang, Xinyong Qi, Xianchao Yang, Yafeng Qiu, Jie Zheng, Feifei Ge, Jinping Zhou
BACKGROUND: Avian influenza viruses represent a growing threat of an influenza pandemic. The co-circulation of multiple H9N2 genotypes over the past decade has been replaced by one predominant genotype-G57 genotype, which displays a changed antigenicity and improved adaptability in chickens. Effective H9N2 subtype avian influenza virus vaccines for poultry are urgently needed. OBJECTIVE: In this study, we constructed H9N2 subtype avian influenza virus-like particle (VLP) and evaluated its protective efficacy in specific pathogen-free (SPF) chickens to lay the foundation for developing an effective vaccine against influenza viruses...
July 28, 2017: Influenza and Other Respiratory Viruses
https://www.readbyqxmd.com/read/28749414/adjuvantation-of-pulmonary-administered-influenza-vaccine-with-gpi-0100-primarily-stimulates-antibody-production-and-memory-b-cell-proliferation
#15
Harshad P Patil, José Herrera Rodriguez, Jacqueline de Vries-Idema, Tjarko Meijerhof, Henderik W Frijlink, Wouter L J Hinrichs, Anke Huckriede
Adjuvants are key components in vaccines, they help in reducing the required antigen dose but also modulate the phenotype of the induced immune response. We previously showed that GPI-0100, a saponin-derived adjuvant, enhances antigen-specific mucosal and systemic antibody responses to influenza subunit and whole inactivated influenza virus (WIV) vaccine administered via the pulmonary route. However, the impact of the GPI-0100 dose on immune stimulation and the immune mechanisms stimulated by GPI-0100 along with antigen are poorly understood...
July 27, 2017: Vaccines
https://www.readbyqxmd.com/read/28737040/potential-of-small-molecule-fungal-metabolites-in-antiviral-chemotherapy
#16
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/28724948/transgenic-chickens-expressing-the-3d8-single-chain-variable-fragment-protein-suppress-avian-influenza-transmission
#17
Sung June Byun, Seong-Su Yuk, Ye-Jin Jang, Hoonsung Choi, Mi-Hyang Jeon, T O Erdene-Ochir, Jung-Hoon Kwon, Jin-Yong Noh, Jeom Sun Kim, Jae Gyu Yoo, Chang-Seon Song
The 3D8 single chain variable fragment (scFv) is a mini-antibody that causes unusual sequence-independent nuclease activity against all types of nucleic acids. We used recombinant lentiviruses to generate transgenic chickens expressing the 3D8 scFv gene under the control of the chicken β-actin promoter. From 420 injected embryos, 200 chicks (G0) hatched and were screened for the 3D8 scFv using PCR, and 15 chicks were identified as transgenic birds expressing the transgene in their semen. The G0 founder birds were mated with wild-type hens to produce seven transgenic chicks (G1)...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28723925/immunologic-response-to-vaccine-challenge-in-pregnant-ptpn22-r620w-carriers-and-non-carriers
#18
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/28720851/microneedle-patch-delivery-of-influenza-vaccine-during-pregnancy-enhances-maternal-immune-responses-promoting-survival-and-long-lasting-passive-immunity-to-offspring
#19
E Stein Esser, Joanna A Pulit-Penaloza, Haripriya Kalluri, Devin McAllister, Elena V Vassilieva, Elizabeth Q Littauer, Nadia Lelutiu, Mark R Prausnitz, Richard W Compans, Ioanna Skountzou
Influenza virus causes life-threatening infections in pregnant women and their newborns. Immunization during pregnancy is the most effective means of preventing maternal and infant mortality/morbidity; however, influenza vaccination rates of pregnant women remain under 50%. Furthermore, the availability of vaccines in low-resource populations is limited. Skin immunization with microneedle patches (MN) is a novel and safe vaccination platform featuring thermostable vaccine formulations. Cold-chain independence and the potential for self-administration can expand influenza vaccination coverage in developing countries...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720097/a-versatile-papaya-mosaic-virus-papmv-vaccine-platform-based-on-sortase-mediated-antigen-coupling
#20
Ariane Thérien, Mikaël Bédard, Damien Carignan, Gervais Rioux, Louis Gauthier-Landry, Marie-Ève Laliberté-Gagné, Marilène Bolduc, Pierre Savard, Denis Leclerc
BACKGROUND: Flexuous rod-shaped nanoparticles made of the coat protein (CP) of papaya mosaic virus (PapMV) have been shown to trigger innate immunity through engagement of toll-like receptor 7 (TLR7). PapMV nanoparticles can also serve as a vaccine platform as they can increase the immune response to fused peptide antigens. Although this approach shows great potential, fusion of antigens directly to the CP open reading frame (ORF) is challenging because the fused peptides can alter the structure of the CP and its capacity to self assemble into nanoparticles-a property essential for triggering an efficient immune response to the peptide...
July 18, 2017: Journal of Nanobiotechnology
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