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norovirus vaccine

Sudhakar Agnihothram, Vineet D Menachery, Boyd L Yount, Lisa C Lindesmith, Trevor Scobey, Alan Whitmore, Alexandra Schäfer, Mark T Heise, Ralph S Baric
Zoonotic viruses circulate as swarms in animal reservoirs and can emerge into human populations causing epidemics that adversely affect public health. Portable, safe, and effective vaccine platforms are needed in the context of these outbreak and emergence situations. In this manuscript, we report the generation and characterization of an alphavirus replicon vaccine platform based on a non-select agent, attenuated Venezuelan equine encephalitis (VEE) virus vaccine strain 3526 (VRP 3526). Using both noroviruses and coronaviruses as model systems, we demonstrate utility of the VRP 3526 platform in generation of recombinant proteins, production of virus like particles, and in vivo efficacy as a vaccine against emergent viruses...
March 14, 2018: Journal of Virology
Mitsutaka Kitano, Myra Hosmillo, Edward Emmott, Jia Lu, Ian Goodfellow
Human norovirus (HuNoV) is a major cause of nonbacterial gastroenteritis worldwide yet, despite their impact on society, vaccines and antivirals are currently lacking. A HuNoV replicon system has been widely applied to the evaluation of antiviral compounds and has thus accelerated the process of drug discovery against HuNoV infection. Rupintrivir, an irreversible inhibitor of the human rhinovirus 3C protease, has been reported to inhibit the replication of the Norwalk virus replicon via the inhibition of the norovirus protease...
March 12, 2018: Antimicrobial Agents and Chemotherapy
Daniel Enosi Tuipulotu, Natalie E Netzler, Jennifer H Lun, Jason M Mackenzie, Peter A White
Norovirus infections are a significant health and economic burden globally, accounting for hundreds of millions of cases of acute gastroenteritis every year. In the absence of an approved norovirus vaccine, there is an urgent need to develop antivirals to treat chronic infections, and provide prophylactic therapy to limit viral spread during epidemics and pandemics. Toll-like receptor (TLR) agonists have been explored widely for their antiviral potential and several are progressing through clinical trials for the treatment of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and as adjuvants for norovirus virus-like particle (VLP) vaccines...
March 12, 2018: Antimicrobial Agents and Chemotherapy
Frank G Sandmann, Laura Shallcross, Natalie Adams, David J Allen, Pietro G Coen, Annette Jeanes, Zisis Kozlakidis, Lesley Larkin, Fatima Wurie, Julie V Robotham, Mark Jit, Sarah R Deeny
Background: Norovirus places a substantial burden on healthcare systems, arising from infected patients, disease outbreaks, beds kept unoccupied for infection control, and staff absences due to infection. In settings with high rates of bed occupancy, opportunity costs arise from patients who cannot be admitted due to beds being unavailable. With several treatments and vaccines against norovirus in development, quantifying the expected economic burden is timely. Methods: The number of inpatients with norovirus-associated gastroenteritis in England were modelled using infectious and non-infectious gastrointestinal Hospital Episode Statistics codes and laboratory reports of gastrointestinal pathogens collected at Public Health England...
February 26, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Mohamad Saifudin Hakim, Hera Nirwati, Abu Tholib Aman, Yati Soenarto, Qiuwei Pan
BACKGROUND: Diarrhea significantly contributes to the global burden of diseases, particularly in developing countries. Rotavirus and norovirus are the most dominant viral agents responsible for diarrheal disease globally. The aim of this review was to conduct a comprehensive assessment of rotavirus and norovirus study in Indonesia. DATA SOURCES: Articles about rotavirus and norovirus surveillance in Indonesia were collected from databases, including PubMed and Google Scholar...
February 14, 2018: World Journal of Pediatrics: WJP
Lisa C Lindesmith, Michael L Mallory, Kari Debbink, Eric F Donaldson, Paul D Brewer-Jensen, Excel W Swann, Timothy P Sheahan, Rachel L Graham, Martina Beltramello, Davide Corti, Antonio Lanzavecchia, Ralph S Baric
Extensive antigenic diversity within the GII.4 genotype of human norovirus is a major driver of pandemic emergence and a significant obstacle to development of cross-protective immunity after natural infection and vaccination. However, human and mouse monoclonal antibody studies indicate that, although rare, antibodies to conserved GII.4 blockade epitopes are generated. The mechanisms by which these epitopes evade immune surveillance are uncertain. Here, we developed a new approach for identifying conserved GII...
January 2018: MSphere
Marieke Bierhoff, Wences Arvelo, Alejandra Estevez, Joe Bryan, John P McCracken, María Reneé López, Beatriz López, Umesh D Parashar, Kim A Lindblade, Aron J Hall
Background: Acute gastroenteritis (AGE) is a leading infectious cause of morbidity worldwide, particularly among children in developing countries. With the decline of rotavirus disease rates following introduction of rotavirus vaccines, the relative importance of norovirus will likely increase. The objectives of this study were to determine the incidence and clinical profile of norovirus disease in Guatemala. Methods: We analyzed data from a population-based surveillance study conducted in Guatemala from 2008-2013...
February 6, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Minesh P Shah, Aron J Hall
Norovirus is a leading cause of childhood vomiting and diarrhea in the United States and globally. Although most illnesses caused by norovirus are self-resolving, severe outcomes may occur from dehydration, including hospitalization and death. A vast majority of deaths from norovirus occur in developing countries. Immunocompromised children are at risk for more severe outcomes. Treatment of norovirus illness is focused on early correction of dehydration and maintenance of fluid status and nutrition. Hand hygiene, exclusion of ill individuals, and environmental cleaning are important for norovirus outbreak prevention and control, and vaccines to prevent norovirus illness are currently under development...
March 2018: Infectious Disease Clinics of North America
Janko van Beek, Miranda de Graaf, Haider Al-Hello, David J Allen, Katia Ambert-Balay, Nadine Botteldoorn, Mia Brytting, Javier Buesa, Maria Cabrerizo, Martin Chan, Fiona Cloak, Ilaria Di Bartolo, Susana Guix, Joanne Hewitt, Nobuhiro Iritani, Miao Jin, Reimar Johne, Ingeborg Lederer, Janet Mans, Vito Martella, Leena Maunula, Georgina McAllister, Sandra Niendorf, Hubert G Niesters, Alexander T Podkolzin, Mateja Poljsak-Prijatelj, Lasse Dam Rasmussen, Gábor Reuter, Gráinne Tuite, Annelies Kroneman, Harry Vennema, Marion P G Koopmans
BACKGROUND: The development of a vaccine for norovirus requires a detailed understanding of global genetic diversity of noroviruses. We analysed their epidemiology and diversity using surveillance data from the NoroNet network. METHODS: We included genetic sequences of norovirus specimens obtained from outbreak investigations and sporadic gastroenteritis cases between 2005 and 2016 in Europe, Asia, Oceania, and Africa. We genotyped norovirus sequences and analysed sequences that overlapped at open reading frame (ORF) 1 and ORF2...
January 25, 2018: Lancet Infectious Diseases
Claire S Waddington, Charlie McLeod, Peter Morris, Asha Bowen, Mark Naunton, Jonathan Carapetis, Keith Grimwood, Roy Robins-Browne, Carl D Kirkwood, Robert Baird, David Green, Ross Andrews, Deborah Fearon, Joshua Francis, Julie A Marsh, Thomas Snelling
INTRODUCTION: Diarrhoeal disease is the second leading cause of death in children under 5 years globally, killing 525 000 annually. Australian Aboriginal and Torres Strait Islander (hereafter Aboriginal) children suffer a high burden of disease. Randomised trials in other populations suggest nitazoxanide accelerates recovery for children with Giardia, amoebiasis, Cryptosporidium, Rotavirus and Norovirus gastroenteritis, as well as in cases where no enteropathogens are found. METHODS AND ANALYSIS: This double blind, 1:1 randomised, placebo controlled trial is investigating the impact of oral nitazoxanide on acute gastroenteritis in hospitalised Australian Aboriginal children aged 3 months to <5 years...
February 1, 2018: BMJ Open
Simone Guadagnucci Morillo, Adriana Luchs, Audrey Cilli, Rita de Cássia Compagnoli Carmona, Maria do Carmo S T Timenetsky
The aims of this study were to monitor human astrovirus (HAstV) infections in patients presenting with acute gastroenteritis in Brazil and to determine the HAstV genotypes of these viruses. From May 2010 to July 2012, a total of 140 samples that were negative for both rotaviruses and noroviruses were randomly selected and tested for the presence of HAstV using an RT-PCR assay specific for the ORF2 region. Viral genotypes were identified and genetic diversity was investigated by sequencing. HAstV infection was detected in 2...
January 30, 2018: Archives of Virology
Martin Chi-Wai Chan, Kirsty Kwok, Lin-Yao Zhang, Kirran N Mohammad, Nelson Lee, Grace C Y Lui, E Anthony S Nelson, Raymond W M Lai, Ting F Leung, Paul K S Chan
We report emerging subtropical bimodal seasonality and alternating predominance of norovirus GII.4 and non-GII.4 genotypes in Hong Kong. GII.4 predominated in summer and autumn months and affected young children, whereas emergent non-GII.4 genotypes predominated in winter months and affected all age groups. This highly dynamic epidemiology should inform vaccination strategies.
April 17, 2018: Emerging Infectious Diseases
Xiaoli Wang, Shuxia Wang, Chao Zhang, Yu Zhou, Pei Xiong, Qingwei Liu, Zhong Huang
Noroviruses (NoVs) are the main pathogens responsible for sporadic and epidemic nonbacterial gastroenteritis, causing an estimated 219,000 deaths annually worldwide. There is no commercially available vaccine for NoVs, due partly to the difficulty in establishing NoV cell culture models. The histo-blood group antigen (HBGA) blocking assay is used extensively to assess the protective potential of candidate vaccine-elicited antibodies, but there is still no widely used cellular evaluation model. In this study, we have established a cell line-based NoV vaccine evaluation model through the construction of human α1,2-fucosyltransferase 2-overexpressing 293T (293T-FUT2) cell lines...
January 5, 2018: Viruses
Maria Malm, Kirsi Tamminen, Suvi Heinimäki, Timo Vesikari, Vesna Blazevic
Norovirus (NoV) is the main cause of acute gastroenteritis worldwide across all age groups. Current NoV vaccine candidates are based on non-infectious highly immunogenic virus-like particles (VLPs) produced in cell cultures in vitro. As NoVs infecting human population are highly divergent, it is proposed that the vaccine should contain at least two different NoV genotypes, potentially affecting the immunogenicity of each other. We investigated the immunogenicity of NoV GII.4 VLPs administered by intramuscular (IM) or intradermal (ID) injections to BALB/c mice either alone or co-delivered with genogroup I (GI) and other genogroup GII VLPs...
December 12, 2017: Vaccine
Vishnu C Damalanka, Yunjeong Kim, Anushka C Galasiti Kankanamalage, Athri D Rathnayake, Nurjahan Mehzabeen, Kevin P Battaile, Scott Lovell, Harry Nhat Nguyen, Gerald H Lushington, Kyeong-Ok Chang, William C Groutas
Acute nonbacterial gastroenteritis caused by noroviruses constitutes a global public health concern and a significant economic burden. There are currently no small molecule therapeutics or vaccines for the treatment of norovirus infections. A structure-guided approach was utilized in the design of a series of inhibitors of norovirus 3CL protease that embody an oxazolidinone ring as a novel design element for attaining optimal binding interactions. Low micromolar cell-permeable inhibitors that display anti-norovirus activity have been identified...
January 1, 2018: European Journal of Medicinal Chemistry
Yingxi Chen, Aron J Hall, Martyn D Kirk
Purpose of Review: Noroviruses are the most common cause of gastroenteritis outbreaks in long-term care facility (LTCFs). This review summarizes the most up-to-date knowledge on norovirus infection in LTCFs with the aim of identifying potential strategies for management. Recent Findings: LTCF residents are at greater risk of norovirus infection. Early identification of norovirus infection and prompt initiation of appropriate supportive therapy are required to reduce morbidity and mortality...
2017: Current Geriatrics Reports
Diego E Gomez, J Scott Weese
A complex community of bacteria, viruses, fungi, protists, and other microorganisms inhabit the gastrointestinal tract of calves and play important roles in gut health and disease. The viral component of the microbiome (the virome) is receiving increasing attention for its role in neonatal calf diarrhea (NCD). Rotavirus and coronavirus have for a long time been associated with NCD and commercial vaccines have been produced against these agents. Recently, several other viruses which may play a role in diarrhea have been discovered in calf fecal samples, mostly by sequence-based methods...
December 2017: Canadian Veterinary Journal. la Revue Vétérinaire Canadienne
Małgorzata Sadkowska-Todys, Andrzej Zieliński, Mirosław P. Czarkowski
PURPOSE OF THE STUDY: This is the next annual analysis of the situation of infectious and parasitic diseases in Poland in 2015 within the framework of the Epidemiological Chronicle of Przegląd Epidemiologiczny - Epidemiological Review. Its purpose is to identify potential threats to the health of populations from infectious diseases occurring in Poland with reference to other parts of the globe. MATERIAL AND METHODS: This paper is an introduction to more detailed studies of the epidemiological situation of selected infectious diseases and summarizes the results of the surveillance of infectious diseases in Poland in 2015...
2017: Przegla̧d Epidemiologiczny
Ichiro Morioka, Naohiro Kamiyoshi, Masahiro Nishiyama, Tomohiko Yamamura, Shogo Minamikawa, Sota Iwatani, Hiroaki Nagase, Kandai Nozu, Noriyuki Nishimura, Mariko Taniguchi-Ikeda, Kazuto Ishibashi, Akihito Ishida, Kazumoto Iijima
BACKGROUND: Acute gastroenteritis (AGE) is a major reason for presentation to pediatric primary emergency medical centers. Because rotavirus vaccines were introduced in November 2011 for voluntary vaccination in Japan, we analyzed the changes in the numbers of AGE patients. METHODS: The number and proportion of patients visiting Kobe children's primary emergency medical center from January 2011 to February 2015 due to AGE, out of all visiting children, were investigated retrospectively...
March 31, 2017: Environmental Health and Preventive Medicine
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
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