Abstract
Major viral structural proteins interact homotypically and/or heterotypically, self-assembling into polyvalent viral capsids that usually elicit strong host immune responses. By taking advantage of such intrinsic features of norovirus capsids, two subviral nanoparticles, 60-valent S60 and 24-valent P24 nanoparticles, as well as various polymers, have been generated through bioengineering norovirus capsid shell (S) and protruding (P) domains, respectively. These nanoparticles and polymers are easily produced, highly stable, and extremely immunogenic, making them ideal vaccine candidates against noroviruses. In addition, they serve as multifunctional platforms to display foreign antigens, self-assembling into chimeric nanoparticles or polymers as vaccines against different pathogens and illnesses. Several chimeric S60 and P24 nanoparticles, as well as P domain-derived polymers, carrying different foreign antigens, have been created and demonstrated to be promising vaccine candidates against corresponding pathogens in preclinical animal studies, warranting their further development into useful vaccines.
Highlights
Noroviruses, members of the Norovirus genus in the family Caliciviridae, are the most important viral pathogens causing acute gastroenteritis, affecting millions of people of all ages worldwide
Through bioengineering the shell (S) and protruding (P) domains of the norovirus capsid protein, polyvalent nanoparticles and polymers/oligomers have been generated as vaccines and vaccine platforms for antigen presentation with wide applications
The P24 nanoparticle itself serves as a potent norovirus vaccine candidate because it is composed of 24 copies of norovirus-neutralizing antigens
Summary
Noroviruses, members of the Norovirus genus in the family Caliciviridae, are the most important viral pathogens causing acute gastroenteritis, affecting millions of people of all ages worldwide. The P domains exhibit oligomeric interactions at the five-fold axis [10] (Figure 1A), suggesting that the P domains can form oligomers or polymers in addition to the P dimers These structural properties of norovirus capsids have been used for design and engineering of full-length and truncated norovirus VP1 proteins to create various nanoparticles [17,18]. Homo- and/or heterotypic interactions are common features of the major structural proteins of other viruses, driving the self-formations of different viral capsids in nature These features have been utilized to produce various noninfectious VLPs or viral capsid-like nanoparticles in vitro by expressing one or more full-length or truncated capsid proteins via various expression systems [19,20]. Several P24/S60 nanoparticle- and polymer-based chimeric vaccine candidates have been generated and characterized, showing high protective efficacies against corresponding viral pathogens or diseases in preclinical animal studies, warranting their future development into useful vaccines
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