![]() VLPs are virus-genome-free particles that resemble the corresponding authentic viruses in size and shape. Several techniques have been applied to NoV vaccine development, including non-replicating virus-like particles (VLPs), P particles, and recombinant adenoviruses ( 11). In 2016, the World Health Organization stated that the development of an NoV vaccine should be considered an absolute priority ( 10). Vaccination is often considered the most cost-effective way to prevent contagious diseases. Population-based surveillance conducted in Zhengding (Hebei, China) and Sanjiang County (Guangxi, China) also confirmed GII.3, GII.4, GII.2, GII.6 and GII.17, as the predominant pathogenic genotypes in children < 5-years of age ( 9). ![]() In 2016, a recombinant norovirus strain, GII.P16-GII.2, led to 79% of the 56 outbreaks, indicating that this strain became a dominant strain in China ( 8). During the winter of 2014-2015, an emergent variant of the GII.17 genotype, Kawasaki 2014, predominated in Hong Kong and outcompeted GII.4 Sydney 2012 in hospitalized cases ( 7). A meta-analysis studied on all AGE caused by NoVs from mainland China before 2017 indicated GII.4 was the dominant strain followed by GII.3, GII.17 ( 6). ![]() The GII.4 genotype, which is recognized as the major cause of large epidemics globally, has undergone epochal evolution with new GII.4 variants emerging every 2-4 years and replacing the previously dominant strains ( 5). However, the NoV burden is dynamic because circulating NoV strains vary annually. Humans are mainly infected by GI, GII, and GIV genogroups ( 4). NoV is a non-enveloped, single-stranded, positive-sense RNA virus, which can be classified into 10 genogroups and over 48 genotypes according to the similarity of RNA-dependent RNA polymerase (RdRp-NS7) or major capsid protein VP1 ( 2, 3). Norovirus (NoV) is a major cause of acute gastroenteritis (AGE), causing 685 million infections and 210,000 deaths worldwide each year ( 1). These results demonstrate that Hexa-VLPs are promising broad-spectrum vaccines to provide immunoprotection against major GI/GII epidemic strains in the future. ![]() Notably, simultaneous immunization with a mixture of six VLPs revealed no immunological interference among the component antigens. 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. 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 (30 µg) adjuvanted with 500 µg of aluminum hydroxide (alum) were selected as the optimal immunization dose after a dose-escalation study. 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. The genetic and antigenic diversity of Norovirus presents challenges for providing broad immune protection, which calls for a multivalent vaccine application. Norovirus is a major cause of acute gastroenteritis worldwide, and no vaccine is currently available. ![]()
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