The Experts below are selected from a list of 276 Experts worldwide ranked by ideXlab platform
Mary K. Estes - One of the best experts on this subject based on the ideXlab platform.
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IV, 1. Structure of Norwalk Virus: the prototype human caliciVirus
Perspectives in Medical Virology, 2020Co-Authors: Andrea Bertolotti-ciarlet, Mary K. Estes, Rong Chen, B. V. Venkataram PrasadAbstract:Publisher Summary Norwalk Virus (NV) is the prototype human Virus in the Caliciviridae , a viral family of non-enveloped positive-sense single-stranded RNA Viruses, and is classified in the genus called “Norwalk-like Viruses” (NLVs). The simple architecture of the NV capsid made from a single major gene product and the ability of the expressed protein to spontaneously assemble into a T = 3 capsid make NV an excellent model system to further the understanding of the structural requirements for the assembly of a T = 3 icosahedral capsid. This chapter describes the structure of NV Virus-like particles (VLPs) and reviews new insights about NV capsid assembly and composition. Biochemical and structural studies of NV VLPs have helped to understand the structure–function relationships of the caliciVirus capsid protein.
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experimental human infection with Norwalk Virus elicits a surrogate neutralizing antibody response with cross genogroup activity
Clinical and Vaccine Immunology, 2015Co-Authors: Rita Czako, David Y Graham, Robert L Atmar, Antone R Opekun, Mark A Gilger, Mary K. EstesAbstract:The human noroViruses (NoVs) are genetically diverse, rapidly evolving RNA Viruses and are the major cause of epidemic gastroenteritis of humans. Serum antibodies that block the interaction of NoVs and NoV Viruslike particles (VLPs) with host attachment factors are considered surrogate neutralizing antibodies in the absence of cell culture and small-animal replication models for the human NoVs. A serological assay for NoV-blocking antibodies was used to assess the breadth of the heterotypic antibody response in the context of an experimental challenge study with a human NoV. Heterotypic histo-blood group antigen (HBGA)-blocking activity against GI.4, GI.7, and GII.4 NoVs increased significantly in the serum of individuals (n = 18) infected with Norwalk Virus (GI.1). Although the fold increases and peak titers of heterotypic antibody were more modest than titers of antibody reactive with the challenge antigen, Norwalk Virus infection elicited a serological rise even against the novel Sydney variant of GII.4 NoVs. These observations indicate that the development of a broadly cross-protective NoV vaccine containing a limited number of genotypes may be possible.
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determination of the 50 human infectious dose for Norwalk Virus
The Journal of Infectious Diseases, 2014Co-Authors: Robert L Atmar, Mary K. Estes, Antone R Opekun, Mark A Gilger, Sue E Crawford, Frederick H Neill, Jennifer Ferreira, Sasirekha Ramani, Heather Hill, David Y GrahamAbstract:Background. NoroViruses are the most common cause of gastroenteritis in the United States. An understanding of the infectious dose of these Viruses is important for risk assessment studies. Methods. Healthy adults were enrolled in a randomized, double-blind, placebo-controlled evaluation of different dosages of Norwalk Virus. Eligible subjects were monitored for clinical gastroenteritis, and infection status was determined. The presence of Virus in vomitus was also assessed. Results. Fifty-seven persons were enrolled; 8 received placebo and an additional 8 persons were considered to be nonsusceptible on the basis of being secretor negative. Twenty-one persons were infected (all blood group O or A), and 67% of those infected developed viral gastroenteritis. The 50% human infectious dose was calculated to be 3.3 reverse transcription polymerase chain reaction units (approximately 1320 genomic equivalents [gEq]) for secretor-positive blood group O or A persons and 7.0 (approximately 2800 gEq) for all secretor-positive persons. The time of illness onset was inversely correlated with inoculum dose. The maximal concentration of Virus shedding was higher for persons with gastroenteritis. Norwalk Virus was identified in 15 of 27 (56%) vomitus samples at a median concentration of 41 000 gEq/mL. Conclusions. The 50% human infectious dose measured is higher than previous estimates and similar to that of other RNA Viruses. Clinical Trials Registration {"type":"clinical-trial","attrs":{"text":"NCT00138476","term_id":"NCT00138476"}}NCT00138476.
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Determination of the 50% Human Infectious Dose for Norwalk Virus
The Journal of Infectious Diseases, 2013Co-Authors: Robert L Atmar, Mary K. Estes, Antone R Opekun, Mark A Gilger, Sue E Crawford, Frederick H Neill, Jennifer Ferreira, Sasirekha Ramani, Heather Hill, David Y GrahamAbstract:Background. NoroViruses are the most common cause of gastroenteritis in the United States. An understanding of the infectious dose of these Viruses is important for risk assessment studies. Methods. Healthy adults were enrolled in a randomized, double-blind, placebo-controlled evaluation of different dosages of Norwalk Virus. Eligible subjects were monitored for clinical gastroenteritis, and infection status was determined. The presence of Virus in vomitus was also assessed. Results. Fifty-seven persons were enrolled; 8 received placebo and an additional 8 persons were considered to be nonsusceptible on the basis of being secretor negative. Twenty-one persons were infected (all blood group O or A), and 67% of those infected developed viral gastroenteritis. The 50% human infectious dose was calculated to be 3.3 reverse transcription polymerase chain reaction units (approximately 1320 genomic equivalents [gEq]) for secretor-positive blood group O or A persons and 7.0 (approximately 2800 gEq) for all secretor-positive persons. The time of illness onset was inversely correlated with inoculum dose. The maximal concentration of Virus shedding was higher for persons with gastroenteritis. Norwalk Virus was identified in 15 of 27 (56%) vomitus samples at a median concentration of 41 000 gEq/mL. Conclusions. The 50% human infectious dose measured is higher than previous estimates and similar to that of other RNA Viruses. Clinical Trials Registration {"type":"clinical-trial","attrs":{"text":"NCT00138476","term_id":"NCT00138476"}}NCT00138476.
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serum hemagglutination inhibition activity correlates with protection from gastroenteritis in persons infected with Norwalk Virus
Clinical and Vaccine Immunology, 2012Co-Authors: Rita Czako, David Y Graham, Robert L Atmar, Antone R Opekun, Mark A Gilger, Mary K. EstesAbstract:ABSTRACT A hemagglutination inhibition (HAI) assay to assess serum antibody responses following Norwalk Virus (NV) infection was developed. HAI activity increased significantly in individuals experimentally infected with NV ( n = 18) and correlated with antibody levels measured in a histo-blood group antigen (HBGA) blocking assay. Prechallenge HAI antibody levels also correlated with protection from the development of gastroenteritis (Mann-Whitney test, P = 0.02). The HAI assay is another assay suitable for the detection of antibody that correlates with protection from Norwalk Virus-associated disease.
Xi Jiang - One of the best experts on this subject based on the ideXlab platform.
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Immunogenicity of Newcastle disease Virus vectors expressing Norwalk Virus capsid protein in the presence or absence of VP2 protein.
Virology, 2015Co-Authors: Shun Chen, Xi Jiang, Kim Y. Green, Siba K. SamalAbstract:Abstract NoroViruses are the most common cause of acute gastroenteritis in humans. Development of an effective vaccine is required for reducing their outbreaks. In order to develop a GI noroVirus vaccine, Newcastle disease Virus vectors, rLaSota and modified rBC, were used to express VP1 protein of Norwalk Virus. Co-expression of VP1 and VP2 proteins by Newcastle disease Virus vectors resulted in enhanced expression of Norwalk Virus VP1 protein and self-assembly of VP1 protein into Virus-like particles. Furthermore, the Norwalk Virus-specific IgG response induced in mice by Newcastle disease Virus vectors was similar to that induced by baculoVirus-expressed Virus-like particles in mice. However, the modified rBC vector in the presence of VP2 protein induced significantly higher levels of cellular and mucosal immune responses than those induced by baculoVirus-expressed VLPs. These results indicate that Newcastle disease Virus has great potential for developing a live Norwalk Virus vaccine by inducing humoral, cellular and mucosal immune responses in humans.
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Application of salivary antibody immunoassays for the detection of incident infections with Norwalk Virus in a group of volunteers.
Journal of Immunological Methods, 2015Co-Authors: Shannon M. Griffin, Xi Jiang, Reagan R. Converse, Juan S. Leon, Timothy J. Wade, Andrey I. EgorovAbstract:Abstract NoroVirus infection is the most common cause of acute gastroenteritis in developed countries. Developing an assay based on a non-invasive biomarker for detecting incident noroVirus infections could improve disease surveillance and epidemiological investigations. This project involved analysis of IgA and IgG noroVirus-specific antibody responses in saliva samples from a Norwalk Virus (Genogroup I, genotype 1 noroVirus) challenge study involving infected and symptomatic, and non-infected asymptomatic individuals. Saliva was collected at the challenge, and two weeks and 40 days post-challenge. Samples were analyzed using the Luminex fluorometric and Meso Scale Discovery (MSD) electrochemiluminescence immunoassays. Recombinant P domains of Norwalk Virus capsid protein, as well as similar recombinant proteins of two genogroup II noroViruses (VA387 and VA207) were used as antigens. Immunoconversions were defined as > 4-fold increase in antibody responses to the noroVirus antigens. Various sample pre-treatment options, buffers, saliva dilution ratios, and data adjustment approaches to control for sample-to-sample variability in saliva composition were compared using the Luminex assay. The results suggest that adjusting responses to the noroVirus antigens for responses to the protein purification tag, glutathione-S-transferase (GST), significantly improved the odds of producing a correct immunoconversion test result. IgG-based tests were more accurate compared to IgA-based tests. At optimal conditions, both Luminex and MSD assays for Norwalk-specific IgG antibodies correctly identified all infected and non-infected individuals. There was no evidence of cross-reactivity of anti-Norwalk Virus antibodies with genogroup II noroViruses. These results suggest that salivary antibody responses can be used for the detection of incident infections with Norwalk Virus in prospective surveys.
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human susceptibility and resistance to Norwalk Virus infection
Nature Medicine, 2003Co-Authors: Lisa C. Lindesmith, Severine Marionneau, Nathalie Ruvoen, Xi Jiang, Lauren Lindblad, Paul W Stewart, Jacques Lependu, Ralph S. BaricAbstract:Infectious diseases have influenced population genetics and the evolution of the structure of the human genome in part by selecting for host susceptibility alleles that modify pathogenesis. NoroVirus infection is associated with ∼90% of epidemic non-bacterial acute gastroenteritis worldwide. Here, we show that resistance to Norwalk Virus infection is multifactorial. Using a human challenge model, we showed that 29% of our study population was homozygous recessive for the α(1,2)fucosyltransferase gene (FUT2) in the ABH histo-blood group family and did not express the H type-1 oligosaccharide ligand required for Norwalk Virus binding. The FUT2 susceptibility allele was fully penetrant against Norwalk Virus infection as none of these individuals developed an infection after challenge, regardless of dose. Of the susceptible population that encoded a functional FUT2 gene, a portion was resistant to infection, suggesting that a memory immune response or some other unidentified factor also affords protection from Norwalk Virus infection.
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Expression of Norwalk Virus capsid protein in transgenic tobacco and potato and its oral immunogenicity in mice (edible vaccineyforeign genesyplants)
1996Co-Authors: Hugh S Mason, Mary K. Estes, Xi Jiang, J Udith, M. Ball, Charles J ArntzenAbstract:Alternatives to cell culture systems for pro- duction of recombinant proteins could make very safe vac- cines at a lower cost. We have used genetically engineered plants for expression of candidate vaccine antigens with the goal of using the edible plant organs for economical delivery of oral vaccines. Transgenic tobacco and potato plants were created that express the capsid protein of Norwalk Virus, a caliciVirus that causes epidemic acute gastroenteritis in hu- mans. The capsid protein could be extracted from tobacco leaves in the form of 38-nm Norwalk Virus-like particles. Recombinant Norwalk Virus-like particle (rNV) was previ- ously recovered when the same gene was expressed in recom- binant baculoVirus-infected insect cells. The capsid protein expressed in tobacco leaves and potato tubers cosedimented in sucrose gradients with insect cell-derived rNV and appeared identical to insect cell-derived rNV on immunoblots of SDSypolyacrylamide gels. The plant-expressed rNV was orally immunogenic in mice. Extracts of tobacco leaf express- ing rNV were given to CD1 mice by gavage, and the treated mice developed both serum IgG and secretory IgA specific for rNV. Furthermore, when potato tubers expressing rNV were fed directly to mice, they developed serum IgG specific for rNV. These results indicate the potential usefulness of plants for production and delivery of edible vaccines. This is an appropriate technology for developing countries where vac- cines are urgently needed.
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expression of Norwalk Virus capsid protein in transgenic tobacco and potato and its oral immunogenicity in mice
Proceedings of the National Academy of Sciences of the United States of America, 1996Co-Authors: Mary K. Estes, Judith M. Ball, Xi Jiang, Hugh S Mason, Jian Jian Shi, Charles J ArntzenAbstract:Abstract Alternatives to cell culture systems for production of recombinant proteins could make very safe vaccines at a lower cost. We have used genetically engineered plants for expression of candidate vaccine antigens with the goal of using the edible plant organs for economical delivery of oral vaccines. Transgenic tobacco and potato plants were created that express the capsid protein of Norwalk Virus, a caliciVirus that causes epidemic acute gastroenteritis in humans. The capsid protein could be extracted from tobacco leaves in the form of 38-nm Norwalk Virus-like particles. Recombinant Norwalk Virus-like particle (rNV) was previously recovered when the same gene was expressed in recombinant baculoVirus-infected insect cells. The capsid protein expressed in tobacco leaves and potato tubers cosedimented in sucrose gradients with insect cell-derived rNV and appeared identical to insect cell-derived rNV on immunoblots of SDS/polyacrylamide gels. The plant-expressed rNV was orally immunogenic in mice. Extracts of tobacco leaf expressing rNV were given to CD1 mice by gavage, and the treated mice developed both serum IgG and secretory IgA specific for rNV. Furthermore, when potato tubers expressing rNV were fed directly to mice, they developed serum IgG specific for rNV. These results indicate the potential usefulness of plants for production and delivery of edible vaccines. This is an appropriate technology for developing countries where vaccines are urgently needed.
Robert L Atmar - One of the best experts on this subject based on the ideXlab platform.
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experimental human infection with Norwalk Virus elicits a surrogate neutralizing antibody response with cross genogroup activity
Clinical and Vaccine Immunology, 2015Co-Authors: Rita Czako, David Y Graham, Robert L Atmar, Antone R Opekun, Mark A Gilger, Mary K. EstesAbstract:The human noroViruses (NoVs) are genetically diverse, rapidly evolving RNA Viruses and are the major cause of epidemic gastroenteritis of humans. Serum antibodies that block the interaction of NoVs and NoV Viruslike particles (VLPs) with host attachment factors are considered surrogate neutralizing antibodies in the absence of cell culture and small-animal replication models for the human NoVs. A serological assay for NoV-blocking antibodies was used to assess the breadth of the heterotypic antibody response in the context of an experimental challenge study with a human NoV. Heterotypic histo-blood group antigen (HBGA)-blocking activity against GI.4, GI.7, and GII.4 NoVs increased significantly in the serum of individuals (n = 18) infected with Norwalk Virus (GI.1). Although the fold increases and peak titers of heterotypic antibody were more modest than titers of antibody reactive with the challenge antigen, Norwalk Virus infection elicited a serological rise even against the novel Sydney variant of GII.4 NoVs. These observations indicate that the development of a broadly cross-protective NoV vaccine containing a limited number of genotypes may be possible.
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determination of the 50 human infectious dose for Norwalk Virus
The Journal of Infectious Diseases, 2014Co-Authors: Robert L Atmar, Mary K. Estes, Antone R Opekun, Mark A Gilger, Sue E Crawford, Frederick H Neill, Jennifer Ferreira, Sasirekha Ramani, Heather Hill, David Y GrahamAbstract:Background. NoroViruses are the most common cause of gastroenteritis in the United States. An understanding of the infectious dose of these Viruses is important for risk assessment studies. Methods. Healthy adults were enrolled in a randomized, double-blind, placebo-controlled evaluation of different dosages of Norwalk Virus. Eligible subjects were monitored for clinical gastroenteritis, and infection status was determined. The presence of Virus in vomitus was also assessed. Results. Fifty-seven persons were enrolled; 8 received placebo and an additional 8 persons were considered to be nonsusceptible on the basis of being secretor negative. Twenty-one persons were infected (all blood group O or A), and 67% of those infected developed viral gastroenteritis. The 50% human infectious dose was calculated to be 3.3 reverse transcription polymerase chain reaction units (approximately 1320 genomic equivalents [gEq]) for secretor-positive blood group O or A persons and 7.0 (approximately 2800 gEq) for all secretor-positive persons. The time of illness onset was inversely correlated with inoculum dose. The maximal concentration of Virus shedding was higher for persons with gastroenteritis. Norwalk Virus was identified in 15 of 27 (56%) vomitus samples at a median concentration of 41 000 gEq/mL. Conclusions. The 50% human infectious dose measured is higher than previous estimates and similar to that of other RNA Viruses. Clinical Trials Registration {"type":"clinical-trial","attrs":{"text":"NCT00138476","term_id":"NCT00138476"}}NCT00138476.
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Determination of the 50% Human Infectious Dose for Norwalk Virus
The Journal of Infectious Diseases, 2013Co-Authors: Robert L Atmar, Mary K. Estes, Antone R Opekun, Mark A Gilger, Sue E Crawford, Frederick H Neill, Jennifer Ferreira, Sasirekha Ramani, Heather Hill, David Y GrahamAbstract:Background. NoroViruses are the most common cause of gastroenteritis in the United States. An understanding of the infectious dose of these Viruses is important for risk assessment studies. Methods. Healthy adults were enrolled in a randomized, double-blind, placebo-controlled evaluation of different dosages of Norwalk Virus. Eligible subjects were monitored for clinical gastroenteritis, and infection status was determined. The presence of Virus in vomitus was also assessed. Results. Fifty-seven persons were enrolled; 8 received placebo and an additional 8 persons were considered to be nonsusceptible on the basis of being secretor negative. Twenty-one persons were infected (all blood group O or A), and 67% of those infected developed viral gastroenteritis. The 50% human infectious dose was calculated to be 3.3 reverse transcription polymerase chain reaction units (approximately 1320 genomic equivalents [gEq]) for secretor-positive blood group O or A persons and 7.0 (approximately 2800 gEq) for all secretor-positive persons. The time of illness onset was inversely correlated with inoculum dose. The maximal concentration of Virus shedding was higher for persons with gastroenteritis. Norwalk Virus was identified in 15 of 27 (56%) vomitus samples at a median concentration of 41 000 gEq/mL. Conclusions. The 50% human infectious dose measured is higher than previous estimates and similar to that of other RNA Viruses. Clinical Trials Registration {"type":"clinical-trial","attrs":{"text":"NCT00138476","term_id":"NCT00138476"}}NCT00138476.
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antibody responses to noroVirus genogroup gi 1 and gii 4 proteases in volunteers administered Norwalk Virus
Clinical and Vaccine Immunology, 2012Co-Authors: Nadim J Ajami, David Y Graham, Antone R Opekun, Mark A Gilger, Frederick H Neill, B Venkataram V Prasad, Meagan A Barry, Berenice Carrillo, Zana Muhaxhiri, Robert L AtmarAbstract:An assay was developed to detect antibodies against two noroVirus proteases among participants in a Norwalk Virus (GI.1) challenge study. Prechallenge seroprevalence was lower against the protease from the homologous GI.1 Virus than against protease from a heterologous GII.4 strain. Seroresponses were detected for 14 of 19 (74%) infected persons.
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serum hemagglutination inhibition activity correlates with protection from gastroenteritis in persons infected with Norwalk Virus
Clinical and Vaccine Immunology, 2012Co-Authors: Rita Czako, David Y Graham, Robert L Atmar, Antone R Opekun, Mark A Gilger, Mary K. EstesAbstract:ABSTRACT A hemagglutination inhibition (HAI) assay to assess serum antibody responses following Norwalk Virus (NV) infection was developed. HAI activity increased significantly in individuals experimentally infected with NV ( n = 18) and correlated with antibody levels measured in a histo-blood group antigen (HBGA) blocking assay. Prechallenge HAI antibody levels also correlated with protection from the development of gastroenteritis (Mann-Whitney test, P = 0.02). The HAI assay is another assay suitable for the detection of antibody that correlates with protection from Norwalk Virus-associated disease.
David Y Graham - One of the best experts on this subject based on the ideXlab platform.
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experimental human infection with Norwalk Virus elicits a surrogate neutralizing antibody response with cross genogroup activity
Clinical and Vaccine Immunology, 2015Co-Authors: Rita Czako, David Y Graham, Robert L Atmar, Antone R Opekun, Mark A Gilger, Mary K. EstesAbstract:The human noroViruses (NoVs) are genetically diverse, rapidly evolving RNA Viruses and are the major cause of epidemic gastroenteritis of humans. Serum antibodies that block the interaction of NoVs and NoV Viruslike particles (VLPs) with host attachment factors are considered surrogate neutralizing antibodies in the absence of cell culture and small-animal replication models for the human NoVs. A serological assay for NoV-blocking antibodies was used to assess the breadth of the heterotypic antibody response in the context of an experimental challenge study with a human NoV. Heterotypic histo-blood group antigen (HBGA)-blocking activity against GI.4, GI.7, and GII.4 NoVs increased significantly in the serum of individuals (n = 18) infected with Norwalk Virus (GI.1). Although the fold increases and peak titers of heterotypic antibody were more modest than titers of antibody reactive with the challenge antigen, Norwalk Virus infection elicited a serological rise even against the novel Sydney variant of GII.4 NoVs. These observations indicate that the development of a broadly cross-protective NoV vaccine containing a limited number of genotypes may be possible.
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determination of the 50 human infectious dose for Norwalk Virus
The Journal of Infectious Diseases, 2014Co-Authors: Robert L Atmar, Mary K. Estes, Antone R Opekun, Mark A Gilger, Sue E Crawford, Frederick H Neill, Jennifer Ferreira, Sasirekha Ramani, Heather Hill, David Y GrahamAbstract:Background. NoroViruses are the most common cause of gastroenteritis in the United States. An understanding of the infectious dose of these Viruses is important for risk assessment studies. Methods. Healthy adults were enrolled in a randomized, double-blind, placebo-controlled evaluation of different dosages of Norwalk Virus. Eligible subjects were monitored for clinical gastroenteritis, and infection status was determined. The presence of Virus in vomitus was also assessed. Results. Fifty-seven persons were enrolled; 8 received placebo and an additional 8 persons were considered to be nonsusceptible on the basis of being secretor negative. Twenty-one persons were infected (all blood group O or A), and 67% of those infected developed viral gastroenteritis. The 50% human infectious dose was calculated to be 3.3 reverse transcription polymerase chain reaction units (approximately 1320 genomic equivalents [gEq]) for secretor-positive blood group O or A persons and 7.0 (approximately 2800 gEq) for all secretor-positive persons. The time of illness onset was inversely correlated with inoculum dose. The maximal concentration of Virus shedding was higher for persons with gastroenteritis. Norwalk Virus was identified in 15 of 27 (56%) vomitus samples at a median concentration of 41 000 gEq/mL. Conclusions. The 50% human infectious dose measured is higher than previous estimates and similar to that of other RNA Viruses. Clinical Trials Registration {"type":"clinical-trial","attrs":{"text":"NCT00138476","term_id":"NCT00138476"}}NCT00138476.
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Determination of the 50% Human Infectious Dose for Norwalk Virus
The Journal of Infectious Diseases, 2013Co-Authors: Robert L Atmar, Mary K. Estes, Antone R Opekun, Mark A Gilger, Sue E Crawford, Frederick H Neill, Jennifer Ferreira, Sasirekha Ramani, Heather Hill, David Y GrahamAbstract:Background. NoroViruses are the most common cause of gastroenteritis in the United States. An understanding of the infectious dose of these Viruses is important for risk assessment studies. Methods. Healthy adults were enrolled in a randomized, double-blind, placebo-controlled evaluation of different dosages of Norwalk Virus. Eligible subjects were monitored for clinical gastroenteritis, and infection status was determined. The presence of Virus in vomitus was also assessed. Results. Fifty-seven persons were enrolled; 8 received placebo and an additional 8 persons were considered to be nonsusceptible on the basis of being secretor negative. Twenty-one persons were infected (all blood group O or A), and 67% of those infected developed viral gastroenteritis. The 50% human infectious dose was calculated to be 3.3 reverse transcription polymerase chain reaction units (approximately 1320 genomic equivalents [gEq]) for secretor-positive blood group O or A persons and 7.0 (approximately 2800 gEq) for all secretor-positive persons. The time of illness onset was inversely correlated with inoculum dose. The maximal concentration of Virus shedding was higher for persons with gastroenteritis. Norwalk Virus was identified in 15 of 27 (56%) vomitus samples at a median concentration of 41 000 gEq/mL. Conclusions. The 50% human infectious dose measured is higher than previous estimates and similar to that of other RNA Viruses. Clinical Trials Registration {"type":"clinical-trial","attrs":{"text":"NCT00138476","term_id":"NCT00138476"}}NCT00138476.
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antibody responses to noroVirus genogroup gi 1 and gii 4 proteases in volunteers administered Norwalk Virus
Clinical and Vaccine Immunology, 2012Co-Authors: Nadim J Ajami, David Y Graham, Antone R Opekun, Mark A Gilger, Frederick H Neill, B Venkataram V Prasad, Meagan A Barry, Berenice Carrillo, Zana Muhaxhiri, Robert L AtmarAbstract:An assay was developed to detect antibodies against two noroVirus proteases among participants in a Norwalk Virus (GI.1) challenge study. Prechallenge seroprevalence was lower against the protease from the homologous GI.1 Virus than against protease from a heterologous GII.4 strain. Seroresponses were detected for 14 of 19 (74%) infected persons.
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serum hemagglutination inhibition activity correlates with protection from gastroenteritis in persons infected with Norwalk Virus
Clinical and Vaccine Immunology, 2012Co-Authors: Rita Czako, David Y Graham, Robert L Atmar, Antone R Opekun, Mark A Gilger, Mary K. EstesAbstract:ABSTRACT A hemagglutination inhibition (HAI) assay to assess serum antibody responses following Norwalk Virus (NV) infection was developed. HAI activity increased significantly in individuals experimentally infected with NV ( n = 18) and correlated with antibody levels measured in a histo-blood group antigen (HBGA) blocking assay. Prechallenge HAI antibody levels also correlated with protection from the development of gastroenteritis (Mann-Whitney test, P = 0.02). The HAI assay is another assay suitable for the detection of antibody that correlates with protection from Norwalk Virus-associated disease.
Ralph S. Baric - One of the best experts on this subject based on the ideXlab platform.
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Norwalk Virus: How infectious is it?
Journal of Medical Virology, 2020Co-Authors: Peter Teunis, Jacques Le Pendu, Sara E Miller, Lisa C. Lindesmith, Ralph S. Baric, Rebecca L CalderonAbstract:NoroViruses are major agents of viral gastroenteritis worldwide. The infectivity of Norwalk Virus, the prototype noroVirus, has been studied in susceptible human volunteers. A new variant of the hit theory model of microbial infection was developed to estimate the variation in Norwalk Virus infectivity, as well as the degree of Virus aggregation, consistent with independent (electron microscopic) observations. Explicit modeling of viral aggregation allows us to express Virus infectivity per single infectious unit (particle). Comparison of a primary and a secondary inoculum showed that passage through a human host does not change Norwalk Virus infectivity. We estimate the average probability of infection for a single Norwalk Virus particle to be close to 0.5, exceeding that reported for any other Virus studied to date. Infected subjects had a dose-dependent probability of becoming ill, ranging from 0.1 (at a dose of 103 NV genomes) to 0.7 (at 108 Virus genomes). A noroVirus dose response model is important for understanding its transmission and essential for development of a quantitative risk model. Norwalk Virus is a valuable model system to study virulence because genetic factors are known for both complete and partial protection; the latter can be quantitatively described as heterogeneity in dose response models. J. Med. Virol. 80:1468–1476, 2008. © 2008 Wiley-Liss, Inc.
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Norwalk Virus how infectious is it
Journal of Medical Virology, 2008Co-Authors: Peter Teunis, Christine L Moe, Pengbo Liu, Jacques Le Pendu, Sara E Miller, Lisa C. Lindesmith, Ralph S. Baric, Rebecca L CalderonAbstract:NoroViruses are major agents of viral gastroenteritis worldwide. The infectivity of Norwalk Virus, the prototype noroVirus, has been studied in susceptible human volunteers. A new variant of the hit theory model of microbial infection was developed to estimate the variation in Norwalk Virus infectivity, as well as the degree of Virus aggregation, consistent with independent (electron microscopic) observations. Explicit modeling of viral aggregation allows us to express Virus infectivity per single infectious unit (particle). Comparison of a primary and a secondary inoculum showed that passage through a human host does not change Norwalk Virus infectivity. We estimate the average probability of infection for a single Norwalk Virus particle to be close to 0.5, exceeding that reported for any other Virus studied to date. Infected subjects had a dose-dependent probability of becoming ill, ranging from 0.1 (at a dose of 103 NV genomes) to 0.7 (at 108 Virus genomes). A noroVirus dose response model is important for understanding its transmission and essential for development of a quantitative risk model. Norwalk Virus is a valuable model system to study virulence because genetic factors are known for both complete and partial protection; the latter can be quantitatively described as heterogeneity in dose response models. J. Med. Virol. 80:1468–1476, 2008. © 2008 Wiley-Liss, Inc.
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human susceptibility and resistance to Norwalk Virus infection
Nature Medicine, 2003Co-Authors: Lisa C. Lindesmith, Severine Marionneau, Nathalie Ruvoen, Xi Jiang, Lauren Lindblad, Paul W Stewart, Jacques Lependu, Ralph S. BaricAbstract:Infectious diseases have influenced population genetics and the evolution of the structure of the human genome in part by selecting for host susceptibility alleles that modify pathogenesis. NoroVirus infection is associated with ∼90% of epidemic non-bacterial acute gastroenteritis worldwide. Here, we show that resistance to Norwalk Virus infection is multifactorial. Using a human challenge model, we showed that 29% of our study population was homozygous recessive for the α(1,2)fucosyltransferase gene (FUT2) in the ABH histo-blood group family and did not express the H type-1 oligosaccharide ligand required for Norwalk Virus binding. The FUT2 susceptibility allele was fully penetrant against Norwalk Virus infection as none of these individuals developed an infection after challenge, regardless of dose. Of the susceptible population that encoded a functional FUT2 gene, a portion was resistant to infection, suggesting that a memory immune response or some other unidentified factor also affords protection from Norwalk Virus infection.
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expression and self assembly of Norwalk Virus capsid protein from venezuelan equine encephalitis Virus replicons
Journal of Virology, 2002Co-Authors: Ralph S. Baric, Lisa C. Lindesmith, Patrick R Harrington, Boyd Yount, Robert E Johnston, Nancy L Davis, Shermalyn R Greene, Fan Chen Tseng, David G KlapperAbstract:The Norwalk Virus (NV) capsid protein was expressed using Venezuelan equine encephalitis Virus replicon particles (VRP-NV1). VRP-NV1 infection resulted in large numbers of recombinant NV-like particles that were primarily cell associated and were indistinguishable from NV particles produced from baculoViruses. Mutations located in the N-terminal and P1 domains of the NV capsid protein ablated capsid self-assembly in mammalian cells.
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systemic mucosal and heterotypic immune induction in mice inoculated with venezuelan equine encephalitis replicons expressing Norwalk Virus like particles
Journal of Virology, 2002Co-Authors: Patrick R Harrington, Boyd Yount, Robert E Johnston, Nancy L Davis, Ralph S. BaricAbstract:Norwalk-like Viruses (NLVs) are a diverse group of single-stranded, nonenveloped, positive-polarity RNA Viruses and are the leading cause of epidemic acute gastroenteritis in the United States. In this study, the major capsid gene of Norwalk Virus, the prototype NLV, has been cloned and expressed in mammalian cells using a Venezuelan equine encephalitis (VEE) replicon expression system. Upon infection of baby hamster kidney (BHK) cells with VEE replicon particles (VRPs), the Norwalk Virus capsid proteins self-assemble to generate high titers of Norwalk Virus-like particles (VLPs) that are morphologically and antigenically analogous to wild-type Norwalk Virus. Mice inoculated subcutaneously with VRPs expressing the Norwalk Virus capsid protein (VRP-NV1) developed systemic and mucosal immune responses to Norwalk VLPs, as well as heterotypic antibody responses to the major capsid protein from another genogroup I NLV strain (NCFL) isolated from a recent outbreak. A second Norwalk Virus capsid clone (NV2) containing three amino acid codon mutations from the NV1 clone was also expressed using VEE replicons (VRP-NV2), but upon infection of BHK cells failed to confer VLP self-assembly. Mice inoculated with VRP-NV2 elicited reduced systemic and mucosal immune responses to Norwalk VLPs, demonstrating the importance and potential utility of endogenous VLP presentation for maximum immune induction. Inoculation with either VRP-NV1 or VRP-NV2 resulted in serum antibody responses far superior to the induction in mice dosed orally with VLPs that were prepared using the VEE-NV1 replicon construct, a regimen similar to current models for NLV vaccination. Expression of NLV VLPs in mammalian cells offers a powerful approach for the design of novel NLV vaccines, either alone or in combination with current vaccination models.