Norovirus Capsid Protein-Derived Nanoparticles and Polymers as Versatile Platforms for Antigen Presentation and Vaccine Development

Tan, Ming; Jiang, Xi

doi:10.3390/pharmaceutics11090472

Cited by 23 publications

(22 citation statements)

References 82 publications

(137 reference statements)

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“…The results showed that the PVNPs bound only 2,3-linked, but not 2,6- or 2,8-linked sialoglycans (Fig. 6(b)), consistent with the known receptor binding nature of their parental H7N9 avian IVs [35,37,38]. Accordingly, the S 60 -HA1 PVNPs agglutinated human RBCs at a high hemagglutination titer of 122 ng/mL (Fig.…”

Section: Ha1ssupporting

confidence: 73%

Bioengineered pseudovirus nanoparticles displaying the HA1 antigens of influenza viruses for enhanced immunogenicity

et al. 2022

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Even with implementation of current influenza vaccines, influenza still claims up to 500,000 lives worldwide annually, indicating a need for a better vaccine strategy. We have developed a technology to generate unique S 60 -HA1 pseudovirus nanoparticles (PVNPs) that display the receptor-binding HA1 domains of influenza viruses. Each self-assembled S 60 -HA1 PVNP consists of a T = 1 icosahedral S 60 nanoparticle that resembles the inner shell of norovirus capsid and 60 surface-displayed HA1 antigens that are excellent vaccine targets. Soluble S 60 -HA1 PVNPs presenting HA1 antigens of H7N9 influenza virus subtypes have been produced efficiently in large amount. Their three-dimensional (3D) structures have been solved by cryogenic electron microscopy. The PVNP-displayed HA1 antigens react with HA-specific antibody, and retain authentic sialic acid binding specificity and hemagglutinate human erythrocytes. The PVNPs are highly immunogenic, eliciting high titers of HA1-specific antibodies in mice and the mouse sera strongly inhibited hemagglutinations of homologous and heterologous influenza virus HA proteins. Therefore, the S 60 -HA1 PVNPs may provide useful reagents to study influenza viruses and offer a potential new vaccine tactic to fight the deadly influenza disease.

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Section: Ha1ssupporting

confidence: 73%

Bioengineered pseudovirus nanoparticles displaying the HA1 antigens of influenza viruses for enhanced immunogenicity

et al. 2022

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“…In terms of applications, it may be possible to engineer this virus into a vaccine candidate that can present some of the conserved antigenic domains but have little to no risk of causing the activity or pathogenesis seen in the VP34/27/25 capsid. Similar systems have precedent in other viruses, such as norovirus capsid-derived nanoparticles [ 58 ].…”

Section: Engineering and Practical Applications Of Astv Structural Proteins And Vlpsmentioning

confidence: 99%

Structural Insights into the Human Astrovirus Capsid

Ykema

Tao

2021

Viruses

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Astroviruses (AstVs) are non-enveloped, positive single-stranded RNA viruses that cause a wide range of inflammatory diseases in mammalian and avian hosts. The T = 3 viral capsid is unique in its ability to infect host cells in a process driven by host proteases. Intercellular protease cleavages allow for viral egress from a cell, while extracellular cleavages allow for the virus to enter a new host cell to initiate infection. High-resolution models of the capsid core indicate a large, exposed region enriched with protease cleavage sites. The virus spike protein allows for binding to target cells and is the major target for naturally occurring and engineered neutralizing antibodies. During maturation, the capsid goes through significant structural changes including the loss of many surface spikes. The capsid interacts with host membranes during the virus life cycle at multiple stages such as assembly, host cell entry and exit. This review will cover recent findings and insights related to the structure of the capsid and its function. Further understanding of the viral capsid structure and maturation process can contribute to new vaccines, gastric therapeutics, and viral engineering applications.

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“…To develop a nonreplicating vaccine for parenteral use, a P 24 -VP8* nanoparticle has been generated as a rotavirus vaccine candidate [ 14 , 15 , 16 ]. Each nanoparticle is composed of a 24 valent P 24 nanoparticle core [ 17 , 18 ] made by 24 norovirus protruding (P) domains and 24 rotavirus VP8* antigens that are displayed on the surface of the nanoparticle.…”

Section: Introductionmentioning

confidence: 99%

A Nanoparticle-Based Trivalent Vaccine Targeting the Glycan Binding VP8* Domains of Rotaviruses

Xia

Huang

Jiang

et al. 2021

Viruses

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Rotavirus causes severe gastroenteritis in children. Although vaccines are implemented, rotavirus-related diarrhea still claims ~200,000 lives annually worldwide, mainly in low-income settings, pointing to a need for improved vaccine tactics. To meet such a public health need, a P24-VP8* nanoparticle displaying the glycan-binding VP8* domains, the major neutralizing antigens of rotavirus, was generated as a new type of rotavirus vaccine. We reported here our development of a P24-VP8* nanoparticle-based trivalent vaccine. First, we established a method to produce tag-free P24-VP8* nanoparticles presenting the VP8*s of P[8], P[4], and P[6] rotaviruses, respectively, which are the three predominantly circulating rotavirus P types globally. This approach consists of a chemical-based protein precipitation and an ion exchange purification, which may be scaled up for large vaccine production. All three P24-VP8* nanoparticle types self-assembled efficiently with authentic VP8*-glycan receptor binding function. After they were mixed as a trivalent vaccine, we showed that intramuscular immunization of the vaccine elicited high IgG titers specific to the three homologous VP8* types in mice. The resulted mouse sera strongly neutralized replication of all three rotavirus P types in cell culture. Thus, the trivalent P24-VP8* nanoparticles are a promising vaccine candidate for parenteral use against multiple P types of predominant rotaviruses.

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Norovirus Capsid Protein-Derived Nanoparticles and Polymers as Versatile Platforms for Antigen Presentation and Vaccine Development

Cited by 23 publications

References 82 publications

Bioengineered pseudovirus nanoparticles displaying the HA1 antigens of influenza viruses for enhanced immunogenicity

Bioengineered pseudovirus nanoparticles displaying the HA1 antigens of influenza viruses for enhanced immunogenicity

Structural Insights into the Human Astrovirus Capsid

A Nanoparticle-Based Trivalent Vaccine Targeting the Glycan Binding VP8* Domains of Rotaviruses

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