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Establishment of Gn Pig Model of HuNoV Infection and Diarrhea
Published in Lijuan Yuan, Vaccine Efficacy Evaluation, 2022
Using logistic regression, the ID50 of the original Norwalk virus (GI.1, 8fIIa isolate) challenge pool was predicted to be around 2.8 × 103 RNA copies in secretor-positive individuals (Atmar et al., 2014). Similarly, in the current study, we estimated the ID50 of Cin-2 to be around 2.51 × 103 RNA copies (Table 3.2). These data show a similar infection potential between the prototypic GI.1 Norwalk virus and the Cin-2.
Order Picornavirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
The 56.6-kDa capsid protein of Norwalk virus (NoV), a member of the only species, namely Norwalk virus, of the Norovirus genus, was produced by the baculovirus-driven expression and demonstrated an ability to self-assemble into empty VLPs similar to native virions in size and appearance (Jiang et al. 1992). These particles induced high levels of Norwalk virus-specific serum antibody in laboratory animals following parenteral inoculation. The early availability of large amounts of the nice NoV VLPs allowed the development of rapid, sensitive, and reliable tests for the diagnosis of Norwalk virus infection as well as the implementation of structural studies. Concerning diagnostics, the new NoV VLPs-based tests were developed (Jiang et al. 1992; Parker et al. 1993; Treanor et al. 1993; Graham et al. 1994), and new insights about the molecular characterization and epidemiology of human caliciviruses have come from application of the new tests (Gray et al. 1993, 1994; Lew et al. 1994; Numata et al. 1994; Parker et al. 1994). Further studies in mice as well as in volunteers demonstrated that the NoV VLPs are a promising mucosal vaccine for NoV infections (Ball et al. 1996, 1998; Guerrero et al. 2001).
Infections in Solid Organ Transplant Recipients Admitted to the Critical Care Unit
Published in Cheston B. Cunha, Burke A. Cunha, Infectious Diseases and Antimicrobial Stewardship in Critical Care Medicine, 2020
Almudena Burillo, Patricia Muñoz, Emilio Bouza
Accordingly, the first step in the management of a patient with fever and diarrhea or abdominal pain should be to try to exclude CMV and C. difficile. If clinical manifestations persist thereafter, a broader differential diagnosis and more sophisticated diagnostic techniques should be considered, as there are reports of SOT recipients with infections caused by Norwalk virus [109], rotavirus [110], adenovirus [111], EBV [112], Cryptosporidium parvum [113], and Isospora belli [114,115], among others. Notwithstanding, the cause of acute diarrhea remains unidentified in one out of three patients [89].
Development of thermostable vaccine adjuvants
Published in Expert Review of Vaccines, 2021
One unique challenge of mucosal vaccination is the need to overcome the natural defense mechanisms at mucosal sites, such as the mucus layer that coats all mucosal surfaces, which protect the host from invasion of foreign pathogens, but also work against successful delivery of vaccines [134]. Many mucosal vaccine formulations thus incorporate mucoadhesive agents, typically synthetic and biopolymers such as chitosan and alginate, to facilitate vaccine retention and delivery. In some cases, these materials can also serve as adjuvants and stabilizing excipients [135]. A lyophilized norovirus VLP vaccine, containing MPL as an adjuvant, chitosan as a mucoadhesive agent and adjuvant, and sucrose and mannitol as stabilizing excipients, showed promise in a Phase 1 clinical trial against Norwalk virus infection. Although thermostability data were not reported, the potential for storage at room temperature was mentioned [136]. Vaccination using an intranasal delivery device significantly reduced the frequencies of Norwalk virus gastroenteritis and Norwalk virus infection in patients [25].
Vaccines against gastroenteritis, current progress and challenges
Published in Gut Microbes, 2020
Hyesuk Seo, Qiangde Duan, Weiping Zhang
GI.1/GII.4 VLP vaccine candidate under development by Takeda is a continuation of monovalent GI.1 VLP (Ligocyte) and is currently the one progressed furthest. GI.1 VLP was initially designed against Norwalk virus. When orally administered without adjuvant, GI.1 VLP showed 83% IgG seroconversion in volunteers.69 Immunogenicity was enhanced when delivered intranasally with adjuvant monophosphoryl lipid A (MPL) and Al(OH)3 at a two-dose regimen.70,71 With GII.4 emerged as the most prevalent genotype, monovalent GI.1 VLP was improved to be a bivalent VLP candidate, by adding consensus GII.4 VLP and administered intramuscularly.72 Intramuscularly immunized adult volunteers developed GI.1- and GII.4-specific antibodies. Interestingly, GI.1/GII.4 VLP-induced antibodies showed an increasing neutralizing activity – antibody blocking histo-blood group antigens (HBGA).73–75 When challenged with a GII.4 NoV strain, the vaccinated group showed reduction of disease severity but unfortunately without significant protection against overall gastroenteritis.76 The lack of protection appeared to be caused mainly by a lower attack rate from the challenge strain (37.5% infection rate), presumably caused by preexisting anti-NoV antibodies in volunteer adults resulted from natural exposure to NoV infections. Efficacy of bivalent GI.1/GII.4 VLP against recurrent infection or infection from heterogenous genotypes needs to be further evaluated.