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Pigs immunized with either VLPs or P particles had postchallenge occurrence of diarrhea reduced by 46

Pigs immunized with either VLPs or P particles had postchallenge occurrence of diarrhea reduced by 46.7% and 60%, respectively, comparable to the 82.9% reduction in diarrhea among animals that had Matrine received natural immunity by prior infection. divided into seven genogroups based on phylogenetic analysis of the entire virus genome or of individual virus genes. Genogroups I (GI) and II (GII) are the most prevalent causes of human disease (Table 1). Each genogroup is further divided into genotypes based phylogenetic analysis of capsid (Figure 1) and polymerase gene sequences [9]. Mutations as well as recombination within and between norovirus genotypes in co-infected patients lead to the periodic emergence of new norovirus variants as well as broad genetic and antigenic diversity of circulating norovirus strains. This genetic diversity poses a potential challenge to the development of a broadly protective norovirus vaccines, as some studies show that immunization and natural infection with a norovirus may elicit immunity specific to that norovirus genogroup [10C11]. The emergence of GII genotype 4 (GII.4) variants that have caused new global pandemics suggests that evolution of the capsid gene can help Matrine the virus escape immunity induced by infection or vaccination [12]. However, serologic studies have shown that many individuals have cross-reactive, putatively protective serum antibodies that recognize new norovirus variants years before such variants emerge [13C14]. Genogroup II (GII) noroviruses cause over 90% of norovirus disease in the US, with GII.4 noroviruses causing 50C80% of disease from year-to-year [2]. Accordingly, while some of the early vaccine efforts were based solely on the first discovered human norovirus, genogroup I genotype I (GI.1), current vaccine development efforts have been directed towards GII.4 noroviruses, with or without the inclusion of a GI norovirus antigen. Open in a separate window Figure 1 Norovirus phylogeny, based on amino acid sequencing of the major capsid protein VP1. Norovirus host range is largely determined by genogroup, although host specificity varies between genotypes for genogroup II (human, porcine) and genogroup IV (human, feline, and canine) noroviruses. Table 1 Norovirus Genogroups and Genotypes Associated With Human Disease culture system for human norovirus infection. Recent breakthroughs have overcome the latter obstacle. We have recently demonstrated that human noroviruses replicate and produce infectious progeny particles in the differentiated enterocytes of human intestinal enteroids, and that based on viral genotype, infection either requires or is enhanced by bile acids [25]. This norovirus culture system has been used to demonstrate successful inactivation of norovirus by heat and radiation as well as abrogation of norovirus infectivity by the addition of human serum containing HBGA-blocking antibodies. Karst and colleagues have also reported Matrine replication of human noroviruses in the BJAB B cell line, which requires the addition of bacterial cofactors supplied either in unfiltered norovirus stool inocula, by addition of heat-inactivated to the B cell media during infection, or by infection of B cells cultured below polarized HT-29 cells grown on transwells; this system has also been used to demonstrate viral inactivation [26C27]. These efforts are enabling the development of assays to determine whether antibodies induced by vaccination can abrogate Mouse monoclonal to PR human norovirus infectivity culture system for human noroviruses. With two norovirus candidate vaccines in human trials and culture of human noroviruses still quite expensive, development of a vaccine based on complete norovirus particles seems unlikely in the immediate future. Select candidate vaccines are discussed individually below. Table 3 Select Human Norovirus Vaccine Candidates [41]. This ease of particle production at scale offers potential cost advantage over VLP-based vaccines and may expand the proportion of the population for whom receipt of a norovirus vaccine would be cost-effective. Additionally, the P particle is at least somewhat permissive to alteration of the norovirus P-domain, a feature that has been exploited to induce immunity to viruses other than norovirus. In one study, chimeric P particles produced by insertion of the rotavirus VP8* into the norovirus VP1 P.