Norovirus Vaccines: Current Clinical Development and Challenges.

Ming Tan

doi:10.3390/pathogens10121641

Abstract

Noroviruses are the major viral pathogens causing epidemic and endemic acute gastroenteritis with significant morbidity and mortality. While vaccines against norovirus diseases have been shown to be of high significance, the development of a broadly effective norovirus vaccine remains difficult, owing to the wide genetic and antigenic diversity of noroviruses with multiple co-circulated variants of various genotypes. In addition, the absence of a robust cell culture system, an efficient animal model, and reliable immune markers of norovirus protection for vaccine evaluation further hinders the developmental process. Among the vaccine candidates that are currently under clinical studies, recombinant VP1-based virus-like particles (VLPs) that mimic major antigenic features of noroviruses are the common ones, with proven safety, immunogenicity, and protective efficacy, supporting a high success likelihood of a useful norovirus vaccine. This short article reviews the recent progress in norovirus vaccine development, focusing on those from recent clinical studies, as well as summarizes the barriers that are being encountered in this developmental process and discusses issues of future perspective.

Highlights

Noroviruses, members of the Norovirus genus in the family Caliciviridae, are a group of nonenveloped, single-stranded, positive-sense RNA viruses
Among the norovirus vaccine candidates that were in clinical research (Table 1), the TAK-214 developed by Takeda Pharmaceuticals International AG [18] is the most studied one
Vaccination significantly decreased incidences of acute gastroenteritis (AGE) (p = 0.006) and viral infection (p = 0.05) caused by Norwalk virus (NV) challenge. In another phase 2a study [25], the bivalent vaccine adjuvanted with monophosphoryl lipid A (MPLA) and aluminum salt was administered intramuscularly for two doses, which reduced vomiting and/or diarrhea caused by challenge with a GII.4

Summary

Introduction

Noroviruses, members of the Norovirus genus in the family Caliciviridae, are a group of nonenveloped, single-stranded, positive-sense RNA viruses. Among the norovirus vaccine candidates that were in clinical research (Table 1), the TAK-214 developed by Takeda Pharmaceuticals International AG [18] is the most studied one This is an adjuvanted VLP-based bivalent vaccine containing two types of VLPs, one from the GI.. GII. represents the predominant genotype that causes most norovirus disease burden globally [19] The inclusion of both GI and GII norovirus antigens intends to broaden its potential protective immunity. Vaccination significantly decreased incidences of AGE (p = 0.006) and viral infection (p = 0.05) caused by NV challenge In another phase 2a study [25], the bivalent vaccine adjuvanted with MPLA and aluminum salt was administered intramuscularly for two doses, which reduced vomiting and/or diarrhea caused by challenge with a GII.. These data suggested that TAK214 vaccine, and likely other norovirus vaccines, could induce certain cross-genotype protective immunity

The Vaxart Norovirus Vaccine

The NVSI Norovirus Vaccine

Findings

The Longkoma Norovirus Vaccine