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norovirus vlp

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
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
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
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
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
Robert L Atmar, Frank Baehner, Jakob P Cramer, Eric Song, Astrid Borkowski, Paul M Mendelman
BACKGROUND: Noroviruses pose a significant public health risk, particularly in very young individuals, older adults, and individuals with underlying conditions. We assessed 2 bivalent norovirus virus-like particle (VLP) vaccine candidate formulations in healthy adults aged 18-49 years. METHODS: Enrolled subjects (n = 454) randomly assigned among 3 groups received intramuscular placebo (saline) or vaccines containing either 15 µg or 50 µg of GI.1 VLP and 50 µg GII...
September 15, 2016: Journal of Infectious Diseases
Yuqi Huo, Xuhui Chen, Lijun Zheng, Jinling Huo, Shanfeng Zhang, Mingchen Wang, Yumei Wang
Genogroup II, genotype 3 noroviruses (GII.3 NoVs) are secondary to GII.4 NoVs in causing acute non-bacterial gastroenteritis worldwide. In our previous study, we found that virus-like particles (VLPs) derived from a GII.3 NoV strain exhibited no binding activity to any salivary and synthetic histo-blood group antigens (HBGAs) tested. In this study, the nucleotide sequence encoding the major capsid protein of another documented GII.3 NoV strain was codon-optimized and synthesized, and the major capsid protein was expressed using recombinant baculovirus virus expression system...
October 2016: Virus Genes
Noelia Carmona-Vicente, David J Allen, Jesús Rodríguez-Díaz, Miren Iturriza-Gómara, Javier Buesa
BACKGROUND: Human noroviruses (NoVs) are the main cause of gastroenteritis worldwide. The most commonly detected NoV strains belong to the genetically diverse GII.4 genotype, with new pandemic variants emerging periodically. Despite extensive efforts, NoV investigation has been hampered by the lack of an effective in vitro cell culture system. However, NoV-derived recombinant virus-like particles (VLPs) resembling empty capsids are good surrogates for analysing NoV antigenicity and virus-ligand interactions...
2016: Virology Journal
F Bucardo, F González, Y Reyes, P Blandón, L Saif, J Nordgren
Information about porcine norovirus (PoNoV), genetically similar to human NoV (HuNoV), is limited from rural areas where household-raised pigs are heavily exposed to faecal material which could facilitate transmission. Histo-blood group antigens (HBGAs) are known susceptibility factors to NoV in humans and in a germfree piglet model but their role in susceptibility in the porcine population remains unknown. This study reports: (i) the seroprevalence and antibody titres to human norovirus (NoV) VLPs in household raised pigs; (ii) the distribution of HBGAs in relation to NoV IgG antibody titres and further characterization by blocking of GII...
May 13, 2016: Zoonoses and Public Health
Kirsi Tamminen, Maria Malm, Timo Vesikari, Vesna Blazevic
Noroviruses (NoVs) account for the majority of diagnosed cases of viral acute gastroenteritis worldwide. Virus-like particle (VLP)-based vaccines against NoV are currently under development. Serum antibodies that block the binding of NoV VLPs to histo-blood group antigens, the putative receptors for NoV, correlate with protection against NoV infection. The role of functional mucosal antibodies in protection is largely unknown, even though the intestinal mucosa is the entry port for NoV. Balb/c mice were immunized intramuscularly (IM) or intranasally (IN) with NoV GII...
June 2016: Viral Immunology
Maria Malm, Kirsi Tamminen, Vesna Blazevic
Norovirus (NoV)-specific serum antibodies bind to NoV-derived virus-like particles (VLPs) and block the binding of VLPs to the host cell attachment factors/receptors, histo-blood group antigens (HBGAs). Blocking antibodies in human sera have been associated with a protection from NoV infection and disease. Studies of experimental NoV VLP-based vaccines measure blocking antibodies in animal sera instead of a traditional virus neutralization assay. This chapter describes the methodology for analyzing blocking antibodies from NoV GII...
2016: Methods in Molecular Biology
Xiang Gao, Malak A Esseili, Zhongyan Lu, Linda J Saif, Qiuhong Wang
UNLABELLED: Human norovirus (HuNoV) genogroup II genotype 4 (GII.4) strains account for about 80% of the gastroenteritis outbreaks in the United States. Contaminated food is a major transmission vehicle for this virus. In humans, pigs, and oysters, histo-blood group antigens (HBGAs) act as attachment factors for HuNoVs. In lettuce, although the virus-like particles (VLPs) of a GII.4 HuNoV were found to bind to cell wall carbohydrates, the exact binding site has not been investigated. Here, we show the presence of HBGA-like carbohydrates in the cell wall of lettuce...
May 15, 2016: Applied and Environmental Microbiology
Noelia Carmona-Vicente, Manuel Fernández-Jiménez, Susana Vila-Vicent, Jesús Rodríguez-Díaz, Javier Buesa
BACKGROUND: Human noroviruses (NoVs) are the main cause of non-bacterial gastroenteritis worldwide. Several studies have linked human susceptibility to NoVs with the expression of histo-blood group antigens (HBGAs). In January 2012, a NoV gastroenteritis outbreak affected a household in Valencia, Spain, and the personal susceptibility to NoV was investigated. METHODS: To reach this aim 8 members of the affected household were recruited for this study and their secretor status, ABO and Lewis antigens were determined...
2016: BMC Infectious Diseases
Stephanie A Parker, Mitchell H Maloy, Jaime Tome-Amat, Cameron L Bardliving, Carl A Batt, Kaylee J Lanz, Jonathon T Olesberg, Mark A Arnold
The production of norovirus virus-like particles (NoV VLPs) displaying NY-ESO-1 cancer testis antigen in Pichia pastoris BG11 Mut(+) has been enhanced through feed-strategy optimization using a near-infrared bioprocess monitor (RTBio(®) Bioprocess Monitor, ASL Analytical, Inc.), capable of monitoring and controlling the concentrations of glycerol and methanol in real-time. The production of NoV VLPs displaying NY-ESO-1 in P. pastoris has potential as a novel cancer vaccine platform. Optimization of the growth conditions resulted in an almost two-fold increase in the expression levels in the fermentation supernatant of P...
March 2016: Biotechnology Progress
Shayla Hesse, Frederick H Neill, Mary K Estes, Sreejesh Shanker, B V Venkataram Prasad, Jennifer Ferreira, Robert L Atmar
The performance of an assay to detect antibodies to a norovirus nonstructural fusion protein, designated VPR and consisting of three proteins (GI.1 virus protein genome-linked [VPg], a virus protease, and an RNA-dependent RNA polymerase), was evaluated. The assay sensitivity and specificity were 74.5% and >95%, respectively, for identifying GI.1 norovirus infection among persons who received either a monovalent GI.1 norovirus virus-like particle (VLP) vaccine or placebo by the intranasal route followed by an oral live GI...
December 9, 2015: Clinical and Vaccine Immunology: CVI
Yuqi Huo, Xin Wan, Tong Ling, Shuo Shen
Noroviruses (NoVs) are the leading cause of non-bacterial acute gastroenteritis worldwide. Due to a lack of cell culture system and animal model, our understanding of NoVs has been lagging behind. In this study, NoV major capsid proteins (VP1) from three different genotypes (GI.2, GII.3 and GII.4) were expressed by using recombinant baculovirus expression system and which led to successful assembly of virus-like particles (VLPs). The receptor binding patterns of three kinds of VLPs were characterized by using synthetic and salivary HBGA-VLP binding assay...
January 2016: Microbial Pathogenesis
Jessica Jenkins Broglie, Brittny Alston, Chang Yang, Lun Ma, Audrey F Adcock, Wei Chen, Liju Yang
Human norovirus is a leading cause of acute gastroenteritis worldwide in a plethora of residential and commercial settings, including restaurants, schools, and hospitals. Methods for easily detecting the virus and for treating and preventing infection are critical to stopping norovirus outbreaks, and inactivation via nanoparticles (NPs) is a more universal and attractive alternative to other physical and chemical approaches. Using norovirus GI.1 (Norwalk) virus-like particles (VLPs) as a model viral system, this study characterized the antiviral activity of Au/CuS core/shell nanoparticles (NPs) against GI...
2015: PloS One
Vesna Blazevic, Maria Malm, Daisuke Arinobu, Suvi Lappalainen, Timo Vesikari
Rotavirus (RV) and norovirus (NoV) are the 2 leading causes of acute viral gastroenteritis worldwide. We have developed a non-live NoV and RV vaccine candidate consisting of NoV virus-like particles (VLPs) and recombinant polymeric RV VP6 protein produced in baculovirus-insect cell expression system. Both components have been shown to induce strong potentially protective immune responses. As VP6 nanotubes are highly immunogenic, we investigated here a possible adjuvant effect of these structures on NoV-specific immune responses in vivo...
March 3, 2016: Human Vaccines & Immunotherapeutics
Xiaoli Wang, Zhiqiang Ku, Wenlong Dai, Tan Chen, Xiaohua Ye, Chao Zhang, Yingyi Zhang, Qingwei Liu, Xia Jin, Zhong Huang
Noroviruses are the main cause of severe viral gastroenteritis, which results in estimated 200,000 deaths each year, primarily in children in the developing world. Genogroup II.4 (GII.4) strains are responsible for the majority of norovirus outbreaks. Enterovirus 71 (EV71), the leading causative agent of hand, foot and mouth disease, has recently been prevalent in Asia-Pacific regions, resulting in significant morbidity and mortality in young children. However, no vaccine is commercially available for either norovirus GII...
October 26, 2015: Vaccine
Yuqi Huo, Xin Wan, Tong Ling, Jie Wu, Zejun Wang, Shengli Meng, Shuo Shen
The newly emerged Norovirus (NoV) Sydney 2012 strain has been sweeping all over the world, causing acute non-bacterial gastroenteritis in adults and children. Due to a lack of cell culture system, virus like particles (VLPs) has been assembled and used as vaccine candidates in preclinical and clinical studies. Expression of the major capsid protein of NoVs using recombinant baculovirus expression system in Sf9 cells leads to formation of VLPs that are morphologically and antigenically similar to true virions...
December 2015: Molecular Immunology
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