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norovirus vlp

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https://www.readbyqxmd.com/read/29140444/safety-and-immunogenicity-of-different-formulations-of-norovirus-vaccine-candidate-in-healthy-adults-a-randomized-controlled-double-blind-clinical-trial
#1
G Leroux-Roels, J P Cramer, P M Mendelman, J Sherwood, R Clemens, A Aerssens, I De Coster, A Borkowski, F Baehner, P Van Damme
Background: We investigated safety and immunogenicity of 1-2 doses of different bivalent virus-like particle (VLP) norovirus vaccine candidate (NoV) formulations in healthy 18-64-year-olds. Methods: On Days 1 and 28 participants (n=420) randomized to 14 equal groups received intramuscular control vaccine (hepatitis A) or one of 11 NoV formulations contained varying dosages of GI.1 and GII.4c genotype VLP antigens with Al(OH)3, and 0μg, 15μg or 50μg MPL. Immunogenicity was assessed on Days 1, 28, 56, 208 and 393...
November 13, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28973354/emergence-of-novel-human-norovirus-gii-17-strains-correlates-with-changes-in-blockade-antibody-epitopes
#2
Lisa C Lindesmith, Jacob F Kocher, Eric F Donaldson, Kari Debbink, Michael L Mallory, Excel W Swann, Paul D Brewer-Jenson, Ralph S Baric
Background: Human norovirus is a significant public health burden with >30 genotypes causing endemic levels of disease and strains from the GII.4 genotype causing serial pandemics as the virus evolves new ligand binding and antigenicity features. During 2014-2015, genotype GII.17 cluster IIIb strains emerged as the leading cause of norovirus infection in select global locations. Comparison of capsid sequences indicate that GII.17 is evolving at previously defined GII.4 antibody epitopes...
August 3, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28866835/comprehensive-characterization-of-a-major-capsid-protein-derived-from-a-documented-gii-6-norovirus-strain
#3
Lijun Zheng, Wenhui Wang, Jinjin Liu, Yuqi Huo, Chuan Qin, Mingchen Wang, Shuo Shen
In this study, we successfully produced VLPs derived from full-length or chimeric VP1 of a documented GII.6 strain. Trypsin digestion of purified VLPs led to total cleavage of VP1, while the integrity of assembled VLPs was not affected. In vitro VLP-histo-blood group antigen (HBGA) binding and binding blockade assays indicated that trypsin digestion enhanced the binding of GII.6 VLPs to salivary HBGAs and that this binding could only be blocked by serum produced against a homologous strain. The data regarding the assembly, morphology and binding patterns of GII...
December 2017: Archives of Virology
https://www.readbyqxmd.com/read/28843813/live-baculovirus-acts-as-a-strong-b-and-t-cell-adjuvant-for-monomeric-and-oligomeric-protein-antigens
#4
Suvi Heinimäki, Kirsi Tamminen, Maria Malm, Timo Vesikari, Vesna Blazevic
Recombinant proteins produced by baculovirus (BV) expression systems contain residual BV after crude purification. We studied adjuvant effect of BV on antibody and T cell responses against two model antigens, monomeric ovalbumin (OVA) protein and oligomeric norovirus (NoV) virus-like particles (VLPs). BALB/c mice were immunized intradermally with OVA alone or OVA formulated with live or inactivated BV, and VLP formulations comprised of chromatographically purified NoV GII.4 VLPs alone or mixed with BV, or of crude purified VLPs containing BV impurities from expression system...
November 2017: Virology
https://www.readbyqxmd.com/read/28802994/expression-and-purification-of-norovirus-virus-like-particles-in-escherichia-coli-and-their-immunogenicity-in-mice
#5
Yuqi Huo, Xin Wan, Tong Ling, Jie Wu, Wenhui Wang, Shuo Shen
Norovirus (NoV) virus like particles (VLPs) produced in Spodoptera frugiperda (Sf9) cells have been tested in human volunteers as vaccine candidate and were shown to be protective against NoV induced acute gastroenteritis. In this study, prevailing Sydney-2012-like NoV major capsid protein gene with or without N-terminal deletions (N26 and N38, 26 and 38 amino acids deleted from N terminus,respectively) were sub-cloned into prokaryotic expression vector, pCold III and pCold IV. Soluble and insoluble proteins were detected for both vectors after induction and higher levels of protein expression were observed for constructs pCold III-N26 and pCold III-N38...
August 9, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28754559/enzymatic-cleavage-promotes-disassembly-of-gii-3-norovirus-virus-like-particles-and-its-binding-to-salivary-histo-blood-group-antigens
#6
Yuqi Huo, Wenhui Wang, Lijun Zheng, Xuhui Chen, Shuo Shen, Mingchen Wang
In this study, we found that addition of fecal extract significantly promoted the binding of GII.3 NoV VLPs to salivary HBGAs. SDS-PAGE analysis indicated that major capsid proteins (VP1) were cleaved into two major bands with molecular weights of 26 and 31kD, respectively. Pretreatment of fecal extract by boiling or addition of protease inhibitor cocktail or type specific protease inhibitor (leupeptin and aprotinin) during incubation all decreased VP1 cleavage and its binding to salivary HBGAs. Trypsin digestion led to cleavage of VP1 and promoted its binding to HBGAs, suggesting that the active enzyme(s) might be trypsin or trypsin-like enzymes...
July 25, 2017: Virus Research
https://www.readbyqxmd.com/read/28668568/norovirus-vaccines-under-development
#7
Yalda Lucero, Roberto Vidal, Miguel O'Ryan G
Noroviruses (NoVs) are one of the leading causes of acute gastroenteritis, including both outbreaks and endemic infections. The development of preventive strategies, including vaccines, for the most susceptible groups (children <5years of age, the elderly and individuals suffering crowding, such as military personnel and travelers) is desirable. However, NoV vaccine development has faced many difficulties, including genetic/antigenic diversity, limited knowledge on NoV immunology and viral cycle, lack of a permissive cell line for cultivation and lack of a widely available and successful animal model...
June 28, 2017: Vaccine
https://www.readbyqxmd.com/read/28640636/cross-reactive-synbody-affinity-ligands-for-capturing-diverse-noroviruses
#8
Nidhi Gupta, John C Lainson, Paul E Belcher, Luhui Shen, Hugh S Mason, Stephen Albert Johnston, Chris W Diehnelt
Noroviruses are the most common cause of acute gastroenteritis in the developed world. Noroviruses are a diverse group of nonenveloped RNA viruses that are continuously evolving. This leads to the rise of immunologically distinct strains of the same genotype on a frequent basis. This diversity presents a unique challenge for detection and tracking of new strains, with the continuous need for new norovirus affinity ligands. Our group developed a family of bivalent synbody affinity ligands using a virus-like particle (VLP) from the 2006 GII...
June 22, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28545100/intranasal-delivery-of-a-bivalent-norovirus-vaccine-formulated-in-an-in-situ-gelling-dry-powder
#9
Jordan P Ball, Michael J Springer, Yawei Ni, Isaac Finger-Baker, Juan Martinez, Jessica Hahn, John F Suber, Ashley V DiMarco, James D Talton, Ronald R Cobb
The global health community is beginning to understand the burden of norovirus-associated disease, which has a significant impact in both developed and developing countries. Norovirus virus like particle (VLP)-based vaccines are currently under development and have been shown to elicit systemic and mucosal immune responses when delivered intranasally. In the present study, we describe the use of a dry powder formulation (GelVac™) with an in situ gelling polysaccharide (GelSite™) extracted from Aloe vera for nasal delivery of a bivalent vaccine formulation containing both GI and GII...
2017: PloS One
https://www.readbyqxmd.com/read/28468886/human-sera-collected-between-1979-and-2010-possess-blocking-antibody-titers-to-pandemic-gii-4-noroviruses-isolated-over-three-decades
#10
Sumit Sharma, Beatrice Carlsson, Rita Czakó, Sirkka Vene, Mats Haglund, Johnny Ludvigsson, Göran Larson, Lennart Hammarström, Stanislav V Sosnovtsev, Robert L Atmar, Kim Y Green, Mary K Estes, Lennart Svensson
The emergence of pandemic GII.4 norovirus (NoV) strains has been proposed to occur due to changes in receptor usage and thereby to lead to immune evasion. To address this hypothesis, we measured the ability of human sera collected between 1979 and 2010 to block glycan binding of four pandemic GII.4 noroviruses isolated in the last 4 decades. In total, 268 sera were investigated for 50% blocking titer (BT50) values of virus-like particles (VLPs) against pig gastric mucin (PGM) using 4 VLPs that represent different GII...
July 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28453838/impact-of-pre-exposure-history-and-host-genetics-on-antibody-avidity-following-norovirus-vaccination
#11
RANDOMIZED CONTROLLED TRIAL
Lisa C Lindesmith, Michael L Mallory, Taylor A Jones, Charles Richardson, Robert R Goodwin, Frank Baehner, Paul M Mendelman, Robert F Bargatze, Ralph S Baric
Background.: Development of high avidity, broadly neutralizing antibodies (Abs) is a priority after vaccination against rapidly evolving, widely disseminated viruses like human norovirus. After vaccination with a multivalent GI.1 and GII.4c norovirus virus-like particle (VLP) vaccine candidate adjuvanted with alum and monophosphoryl lipid A (MPL), blockade Ab titers peaked early, with no increase in titer following a second vaccine dose. Methods.: Blockade Ab relative avidity was evaluated by measuring the slope of blockade Ab neutralization curves...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28364126/carbon-dots-antiviral-functions-against-noroviruses
#12
Xiuli Dong, Marsha M Moyer, Fan Yang, Ya-Ping Sun, Liju Yang
This study reported the first assessment of carbon dots' (CDots) antiviral activity to human norovirus virus-like-particles (VLPs), GI.1 and GII.4 VLPs. CDots with different surface passivation molecules, 2,2'-(ethylenedioxy)bis(ethylamine) (EDA)-CDots and 3-ethoxypropylamine (EPA)-CDots, were synthesized and evaluated. The results indicated both EDA- and EPA- CDots were highly effective to inhibit both strains of VLPs' bindings to histo-blood group antigens (HBGA) receptors on human cells at CDots concentration of 5 µg/mL, with EDA-CDots achieving 100% inhibition and EPA CDots achieving 85-99% inhibition...
March 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28294600/histo-blood-group-antigen-presentation-is-critical-for-binding-of-norovirus-vlp-to-glycosphingolipids-in-model-membranes
#13
Waqas Nasir, Martin Frank, Angelika Kunze, Marta Bally, Francisco Parra, Per-Georg Nyholm, Fredrik Höök, Göran Larson
Virus entry depends on biomolecular recognition at the surface of cell membranes. In the case of glycolipid receptors, these events are expected to be influenced by how the glycan epitope close to the membrane is presented to the virus. This presentation of membrane-associated glycans is more restricted than that of glycans in solution, particularly because of orientational constraints imposed on the glycolipid through its lateral interactions with other membrane lipids and proteins. We have developed and employed a total internal reflection fluorescence microscopy-based binding assay and a scheme for molecular dynamics (MD) membrane simulations to investigate the consequences of various glycan presentation effects...
May 19, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28249841/b-cell-responses-to-intramuscular-administration-of-a-bivalent-virus-like-particle-human-norovirus-vaccine
#14
Sasirekha Ramani, Frederick H Neill, Jennifer Ferreira, John J Treanor, Sharon E Frey, David J Topham, Robert R Goodwin, Astrid Borkowski, Frank Baehner, Paul M Mendelman, Mary K Estes, Robert L Atmar
Human noroviruses (HuNoVs) are a leading cause of acute gastroenteritis worldwide. A virus-like particle (VLP) candidate vaccine induces the production of serum histo-blood group antigen (HBGA)-blocking antibodies, the first identified correlate of protection from HuNoV gastroenteritis. Recently, virus-specific IgG memory B cells were identified to be another potential correlate of protection against HuNoV gastroenteritis. We assessed B-cell responses following intramuscular administration of a bivalent (genogroup I, genotype 1 [GI...
May 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28219831/expression-and-characterization-of-the-major-capsid-protein-derived-from-a-gii-6-norovirus-strain-isolated-in-china
#15
Yuqi Huo, Lijun Zheng, Xuhui Chen, Lili Ge, Yumei Wang
The objective of this study was to express and characterize the major capsid protein (VP1) of a GII.6 Norovirus (NoV)strain isolated in China. The newly identified GII.6 NoV strain was isolated from a five-year old boy presenting acute gastroenteritis. The genome of the GII.6 strain was 7550 nucleotides in length, excluding the poly-adenylation tail. Multiple sequence alignment and phylogenetic analysis based on deduced VP1 amino acid sequences from different genotypes indicated close relationship between GII...
April 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/27689099/rotavirus-recombinant-vp6-nanotubes-act-as-an-immunomodulator-and-delivery-vehicle-for-norovirus-virus-like-particles
#16
Maria Malm, Kirsi Tamminen, Suvi Lappalainen, Timo Vesikari, Vesna Blazevic
We have recently shown that tubular form of rotavirus (RV) recombinant VP6 protein has an in vivo adjuvant effect on the immunogenicity of norovirus (NoV) virus-like particle (VLP) vaccine candidate. In here, we investigated in vitro effect of VP6 on antigen presenting cell (APC) activation and maturation and whether VP6 facilitates NoV VLP uptake by these APCs. Mouse macrophage cell line RAW 264.7 and dendritic cell line JAWSII were used as model APCs. Internalization of VP6, cell surface expression of CD40, CD80, CD86, and major histocompatibility class II molecules, and cytokine and chemokine production were analyzed...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27573255/type-specific-and-cross-reactive-antibodies-and-t-cell-responses-in-norovirus-vlp-immunized-mice-are-targeted-both-to-conserved-and-variable-domains-of-capsid-vp1-protein
#17
Maria Malm, Kirsi Tamminen, Timo Vesikari, Vesna Blazevic
Norovirus (NoV)-specific antibodies, which block binding of the virus-like particles (VLPs) to the cell receptors are conformation dependent and directed towards the most exposed domain of the NoV capsid VP1 protein, the P2 domain. Limited data are available on the antibodies directed to other domains of the VP1, and even less on the NoV VP1-specific T cell epitopes. In here, BALB/c mice were immunized with six VLPs derived from NoV GII.4-1999, GII.4-2009 (New Orleans), GII.4-2012 (Sydney), GII.12, GI.1, and G1...
October 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27554301/effects-of-disinfectants-against-norovirus-virus-like-particles-predict-norovirus-inactivation
#18
Jun Sato, Motohiro Miki, Hiromi Kubota, Jun Hitomi, Hajime Tokuda, Reiko Todaka-Takai, Kazuhiko Katayama
Human noroviruses (NoVs) are a major cause of epidemic and sporadic acute gastroenteritis worldwide. Public and personal hygiene is one of the most important countermeasures for preventing spread of NoV infection. However, no a practicable cell culture system for NoV had been developed, initial tests of the virucidal effectiveness of anti-NoV disinfectants and sanitizers have been performed using surrogate viruses. In this study, NoV virus-like particles (VLPs) were used as a new surrogate for NoVs and a method for evaluating NoV inactivation using them developed...
September 2016: Microbiology and Immunology
https://www.readbyqxmd.com/read/27521750/chimeric-vlps-with-gii-3-p2-domain-in-a-backbone-of-gii-4-vp1-confers-novel-hbga-binding-ability
#19
Yuqi Huo, Wenhui Wang, Tong Ling, Xin Wan, Li Ding, Shuo Shen, Jinling Huo, Shanfeng Zhang, Mingchen Wang, Yumei Wang, Yubing Liu
Noroviruses (NoVs) are a leading cause of non-bacterial acute gastroenteritis worldwide. The prevalence of Genogroup II, genotype 3 (GII.3) NoVs is secondary to the epidemic GII.4 strains which show broad spectrum binding activities against multiple types of histo-blood group antigens (HBGAs). In our previous study it was found that GII.3 NoV VLPs exhibited no binding activity to all synthetic and salivary HBGAs tested. To determine the compatibility of P2 domains between different genotypes and its effect over the binding specificity to HBGAs, we swapped the P2 domain of a GII...
September 15, 2016: Virus Research
https://www.readbyqxmd.com/read/27355511/frequent-use-of-the-iga-isotype-in-human-b-cells-encoding-potent-norovirus-specific-monoclonal-antibodies-that-block-hbga-binding
#20
Gopal Sapparapu, Rita Czakó, Gabriela Alvarado, Sreejesh Shanker, B V Venkataram Prasad, Robert L Atmar, Mary K Estes, James E Crowe
Noroviruses (NoV) are the most common cause of non-bacterial acute gastroenteritis and cause local outbreaks of illness, especially in confined situations. Despite being identified four decades ago, the correlates of protection against norovirus gastroenteritis are still being elucidated. Recent studies have shown an association of protection with NoV-specific serum histo-blood group antigen-blocking antibody and with serum IgA in patients vaccinated with NoV VLPs. Here, we describe the isolation and characterization of human monoclonal IgG and IgA antibodies against a GI...
June 2016: PLoS Pathogens
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