6-Valent Virus-Like Particle-Based Vaccine Induced Potent and Sustained Immunity Against Noroviruses in Mice

Abstract

Norovirus is a major cause of acute gastroenteritis worldwide, and no vaccine is currently available. The genetic and antigenic diversity of Norovirus presents challenges for providing broad immune protection, which calls for a multivalent vaccine application. In this study, we investigated the possibility of developing a virus-like particle (VLP)-based 6-valent Norovirus vaccine candidate (Hexa-VLPs) that covers GI.1, GII.2, GII.3, GII.4, GII.6, and GII.17 genotypes. Hexa-VLPs (30 µg) adjuvanted with 500 µg of aluminum hydroxide (alum) were selected as the optimal immunization dose after a dose-escalation study. Potent and long-lasting blockade antibody responses were induced by 2-or 3-shot Hexa-VLPs, especially for the emerging GII.P16-GII.2 and GII.17 (Kawasaki 2014) genotypes. Hexa-VLPs plus alum elicited Th1/Th2 mixed yet Th2-skewed immune responses, characterized by an IgG1-biased subclass profile and significant IL-4+ T-cell activation. Notably, simultaneous immunization with a mixture of six VLPs revealed no immunological interference among the component antigens. These results demonstrate that Hexa-VLPs are promising broad-spectrum vaccines to provide immunoprotection against major GI/GII epidemic strains in the future.

Engineered Norovirus-Derived Nanoparticles as a Plug-and-Play Cancer Vaccine Platform

“…Norovirus (Nov) is a single positive-stranded RNA virus that is currently the main viral pathogen causing acute gastroenteritis in most countries worldwide. , The norovirus genome is approximately 7500 nucleotides in length and consists of three open reading frames (ORFs). ORF2 encodes the major capsid protein VP1, , which assembles into 38–40 nm (180 subunits) or 23 nm (60 subunits) Nov VLPs after being expressed in Pichia pastoris expression systems , and baculovirus expression systems. , Interestingly, structural analysis of the Nov capsid via X-ray crystallography revealed that full-length VP1 consists of an N-terminal shell (S) domain connected by a short, flexible hinge to a C-terminus-protruding (P) domain . Structural proteins lacking the P domain can self-assemble into NPs with diameters slightly less than 30 nm, suggesting that the S domain alone shows the potential to present a protein antigen of interest in a nanoparticle structure .…”

“…20,21 The norovirus genome is approximately 7500 nucleotides in length and consists of three open reading frames (ORFs). ORF2 encodes the major capsid protein VP1, 22,23 which assembles into 38−40 nm (180 subunits) or 23 nm (60 subunits) Nov VLPs after being expressed in Pichia pastoris expression systems 24,25 and baculovirus expression systems. 26,27 Interestingly, structural analysis of the Nov capsid via X-ray crystallography revealed that full-length VP1 consists of an N-terminal shell (S) domain connected by a short, flexible hinge to a C-terminus-protruding (P) domain.…”

Antiviral Activities of Asarones and Rhizomes of Acorus gramineus on Murine Norovirus

“…NVs belonging to the Caliciviridae family can be classified into 10 genogroups (GI–GX) and 48 genotypes [ 3 ]. Among the genogroups, GI, GII, GIV, GVIII, and GIX are known to infect humans, and the GII.4 genotype accounts for the majority of outbreaks worldwide [ 3 , 4 , 5 ]. Human norovirus (HuNV) initiates infection by binding to a receptor, histo-blood group antigen (HBGA), using the protruding (P) domain of the capsid protein VP1 [ 6 ].…”