Recent advances in human norovirus research and implications for candidate vaccines

ABSTRACT

Introduction

Noroviruses are a leading cause of acute gastroenteritis worldwide. An estimated 21 million illnesses in the United States and upwards of 684 million illnesses worldwide are attributed to norovirus infection. There are no licensed vaccines to prevent norovirus, but several candidates are in development.

Areas covered

We review recent advances in molecular epidemiology of noroviruses, immunology, and in-vitro cultivation of noroviruses using human intestinal enteroids. We also provide an update on the status of norovirus vaccine candidates.

Expert opinion

Molecular epidemiological studies confirm the tremendous genetic diversity of noroviruses, the continuous emergence of new recombinant strains, and the predominance of GII.4 viruses worldwide. Duration of immunity, extent of cross protection between different genotypes, and differences in strain distribution for young children compared with adults remain key knowledge gaps. Recent discoveries regarding which epitopes are targeted by neutralizing antibodies using the novel in vitro culture of human noroviruses in human intestinal enteroids are enhancing our understanding of mechanisms of protection and providing guidance for vaccine development. A future norovirus vaccine has the potential to substantially reduce the burden of illnesses due to this ubiquitous virus.

KEYWORDS:

• Norovirus
• acute gastroenteritis
• vaccine development
• immunology

Article highlights

• Noroviruses cause an estimated 684 million illnesses of acute gastroenteritis worldwide resulting in approximately $60 billion in societal costs.

• There are no vaccines currently licensed to prevent norovirus infection or disease, although several candidate vaccines are in clinical and pre-clinical trials.

• Increased surveillance efforts have helped to identify and characterize several novel genotypes and updated norovirus classification now recognizes 5 genogroups infecting humans with the majority of infections associated with GI and GII viruses.

• GII.4 strains have been the predominant strains over the past several decades, but in recent years some geographic regions have seen the emergence and predominance of non-GII.4 strains.

• The routine use of dual typing of the capsid and polymerase regions of norovirus strains has helped identify and highlight the role of recombination in the evolution of noroviruses.

• The identification of conserved B and T cell antibody binding sites helps inform vaccine development, particularly characterization of broadly neutralizing epitopes against different strains.

• The duration of natural or vaccine-induced immunity remains unclear, as does the extent of cross protection against different genogroups or genotypes. Birth cohort studies may help elucidate some of these knowledge gaps.

• Human intestinal enteroids can now be used to culture noroviruses and are a valuable tool for evaluating the immunology of noroviruses and for measuring neutralizing antibodies after vaccination.

Author contirubtion

JC wrote the manuscript in consultation with JV, AH, UP. All authors provided critical feedback and revision of the manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Disclaimer

The findings and conclusion in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was partly funded by the intramural food safety program at the Centers for Disease Control and Prevention (CDC).