Prospects and Challenges in the Development of a Norovirus Vaccine

Abstract

Purpose: Norovirus is the leading cause of acute epidemic gastroenteritis among children under the age of 5 years and adults in the United States and in adults worldwide, accounting for an estimated 20% of episodes of acute gastroenteritis across all ages. No effective vaccine is presently available. This article provides an overview of the current state of norovirus vaccine development, emphasizing barriers and challenges in the development of an effective vaccine, correlates of protection used to assess vaccine efficacy, and the results of clinical trials of the major candidate vaccines.

Methods: We performed an unstructured literature review of published articles listed in PubMed in the field of norovirus vaccine development, with an emphasis on studies in humans.

Findings: Two candidate vaccines have reached clinical trials, and a number of other candidates are in the preclinical stages of development. Multivalent vaccination may be effective in inducing broadly neutralizing antibodies protective against challenge with novel and heterologous norovirus strains. Most identified correlates of protection have not been validated in large-scale challenge studies, nor have the degrees to which these correlates covary been assessed.

Implications: Immune correlates of protection against norovirus infection need to be further developed to facilitate additional studies of the tolerability and efficacy of candidate norovirus vaccines in humans.

Keywords: acute gastroenteritis; calicivirus; norovirus; prevention; vaccine.

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.