Norwalk virus-like particles as vaccines - PubMed (original) (raw)
Review
Norwalk virus-like particles as vaccines
Melissa Herbst-Kralovetz et al. Expert Rev Vaccines. 2010 Mar.
Abstract
Noroviruses (NoV) cause the great majority of epidemic nonbacterial gastroenteritis in humans. Expression of the capsid protein in recombinant systems, including insect and plant cells, yields assembly of virus-like particles (VLPs) that mimic the antigenic structure of authentic virions, and are relatively acid- and heat-stable. Norwalk virus (NV), the prototype NoV, has been studied extensively, and Norwalk virus-like particles (NVLPs) produced in insect cells and plants are immunogenic in mice and humans when delivered orally, stimulating the production of systemic and mucosal anti-NV antibodies. NVLPs are also highly immunogenic when delivered intranasally, provoking antibodies at levels similar to orally delivered VLP at much lower doses. Oral and nasal delivery of NVLPs efficiently produces antibodies at distal mucosal sites, which suggests that NVLPs could be used to deliver heterologous peptide antigens by production of genetic fusion chimeric capsid proteins. Examination of norovirus VLP surface structures and receptor binding motifs facilitates identification of potential sites for insertion of foreign peptides that will minimally affect the efficiency of VLP assembly and receptor binding. Thus, there is strong potential to use norovirus VLPs as vaccine-delivery vehicles.
Figures
Figure 1. Virus-like particles assembled from Norwalk virus capsid protein expressed in plants
Norwalk virus capsid protein was transiently expressed in leaves of Nicotiana benthamiana using a geminiviral vector [16]. The leaf extract was sedimented on a sucrose gradient, and the peak virus-like particle fraction collected and examined by transmission electron microscopy following negative staining with uranyl acetate. The particles observed are very similar to those expressed in insect cells [21].
References
- Fankhauser RL, Noel JS, Monroe SS, Ando T, Glass RI. Molecular epidemiology of “Norwalk-like viruses” in outbreaks of gastroenteritis in the United States. J. Infect. Dis. 1998;178(6):1571–1578. • Documents the prevalence of viral gastroenteritis caused by noroviruses (NoV) in the USA.
- Patel MM, Hall AJ, Vinje J, Parashar UD. Noroviruses: a comprehensive review. J. Clin. Virol. 2009;44(1):1–8. - PubMed
- Koopmans M. Progress in understanding norovirus epidemiology. Curr. Opin Infect. Dis. 2008;21(5):544–552. - PubMed
- Lopman B, Vennema H, Kohli E, et al. Increase in viral gastroenteritis outbreaks in Europe and epidemic spread of new norovirus variant. Lancet. 2004;363(9410):682–688. • Documents the prevalence of viral gastroenteritis caused by NoV in Europe.
Website
- Norwalk Vaccine Study. http://clinicaltrials.gov/ct2/show/NCT00973284?term=ligocyte&rank=2.
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