Progress on norovirus vaccine research: public health considerations and future directions

Abstract

Noroviruses are the leading cause of foodborne illness worldwide, account for approximately one-fifth of acute gastroenteritis (AGE) cases globally, and cause a substantial economic burden. Candidate norovirus vaccines are in development, but there is currently no licensed vaccine. Areas covered: Noroviruses cause approximately 684 million cases and 212,000 deaths per year across all age groups, though burden estimates vary by study and region. Challenges to vaccine research include substantial and rapidly evolving genetic diversity, short-term and homotypic immunity to infection, and the absence of a single, well-established correlate of protection. Nonetheless, several norovirus vaccine candidates are currently in development, utilizing virus-like particles (VLPs), P particles, and recombinant adenoviruses. Of these, a bivalent GI.1/GII.4 VLP-based intramuscular vaccine (Phase IIb) and GI.1 oral vaccine (Phase I) are in clinical trials. Expert Commentary: A norovirus vaccine should target high-risk populations, including the young and the elderly, and protect them against the most common circulating norovirus strains. A norovirus vaccine would be a powerful tool in the prevention and control of norovirus while lessening the burden of AGE worldwide. However, more robust burden and cost estimates are needed to justify investments in and guide norovirus vaccine development.

Primary care physician knowledge, attitudes, and diagnostic testing practices for norovirus and acute gastroenteritis

“…Our survey results indicate that providers support vaccine introduction and do not believe their patients receive too many vaccines. With norovirus vaccine candidates currently in phase I and II clinical trials [5], this support will facilitate new vaccine introduction in future years.…”

“…The burden of disease is substantial; children <5 years of age have the highest rates of norovirus-associated medical visits [2], while older adults are at greatest risk for norovirus-associated deaths [3,4]. Several candidate vaccines are currently in clinical trials, including an oral tablet vaccine that recently reported phase I results from a bivalent GI.1/GII.4 formulation in adults, as well as a bivalent GI.1/GII.4 consensus sequence virus-like particle intramuscular vaccine candidate that has conducted phase II trials in children, adults, and the elderly [5][6][7]. Despite the large burden of disease, practicing physicians may not be aware of the importance of norovirus as a cause of AGE.…”

Recent Progress on the Versatility of Virus-Like Particles

“…Finally, prophylactic and therapeutic vaccines targeting different viruses, such as rotavirus, norovirus, and enterovirus, have evolved with the maturity of VLP vaccine technology (Table 1). These new vaccines are expected to prevent more human diseases [76,101,102].…”

Dynamics in the murine norovirus capsid revealed by high-resolution cryo-EM

“…In addition to providing insights about fundamental virus biology, hsMNV also offers a platform for the development of a thermostabilised vaccine against noroviruses. Most norovirus vaccine candidates under development are VLPs [32]. VLPs lack a viral genome, which can provide stabilising interactions with the capsid [33].…”