10 Scopus citations

Abstract

Gastroenteritis (GE) and its associated diarrheal diseases remain as one of the top causes of death in the world. Noroviruses (NoVs) are a group of genetically diverse RNA viruses that cause the great majority of nonbacterial gastroenteritis in humans. However, there is still no vaccine licensed for human use to prevent NoV GE. The lack of a tissue culture system and a small animal model further hinders the development of NoV vaccines. Virus-like particles (VLPs) that mimic the antigenic architecture of authentic virions, however, can be produced in insect, mammalian, and plant cells by the expression of the capsid protein. The particulate nature and high-density presentation of viral structure proteins on their surface render VLPs as a premier vaccine platform with superior safety, immunogenicity, and manufacturability. Therefore, this chapter focuses on the development of effective NoV vaccines based on VLPs of capsid proteins. The expression and structure of NoV VLPs, especially VLPs of Norwalk virus, the prototype NoV, are extensively discussed. The ability of NoV VLPs in stimulating a potent systemic and mucosal anti-NoV immunity through oral and intranasal delivery in mice is presented. The advantages of plant expression systems as a novel production platform for VLP-based NoV vaccines are discussed in light of their cost-effectiveness, production speed, and scalability. Recent achievements from the first successful demonstration of NoV VLP production in plant expression system under the current Good Manufacture Practice (cGMP) regulation by the US Food and Drug Administration (FDA) are detailed. Moreover, results of human clinical trials demonstrating the safety and efficacy of insect and plant-derived NoV VLPs are also presented. Due to the diversity of capsid protein among different NoV strains and its rapid antigenic drift, we speculate that vaccine development should focus on multivalent VLP vaccines derived from capsid proteins of the most prevalent strains. With the very recent approval of the first plant-made biologics by the FDA, we also speculate that plant-based production systems will play an important role in manufacturing such multivalent VLP-based NoV vaccines.

Original languageEnglish (US)
Title of host publicationFrom Prophylaxis to Therapy
PublisherSpringer-Verlag Wien
Pages153-181
Number of pages29
Volume1
ISBN (Electronic)9783709114193
ISBN (Print)3709114187, 9783709114186
DOIs
StatePublished - Oct 1 2013

ASJC Scopus subject areas

  • Medicine(all)
  • Immunology and Microbiology(all)

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