Epidemiologic challenges in norovirus vaccine development

Abstract

Norovirus is the leading cause of acute gastroenteritis (AGE) worldwide. In the United States norovirus is estimated to cause 19-21 million illnesses, 1.7-1.9 million outpatient visits, 56,000-71,000 hospitalizations, and 570-800 deaths annually. Through direct costs and loss of productivity, norovirus disease cost the US economy more than $5.5 billion annually. Due to the lack of available therapies to treat norovirus infections and their highly infectious nature, preventing norovirus illness through vaccination is an appealing strategy. Currently, several norovirus vaccines are in development, including five vaccines in preclinical trials, an oral monovalent vaccine (Vaxart, Inc.) that recently completed a phase IB clinical trial, and a bivalent intramuscular vaccine (Takeda Pharmaceutical Company Limited) in a phase IIB clinical trial. However, no norovirus vaccines are currently available on the market. In this commentary we aim to describe some of the barriers faced in norovirus vaccine development, particularly focusing on vaccine effectiveness and defining the target population.

No evidence of an increase in the incidence of norovirus gastroenteritis hospitalizations in young children after the introduction of universal rotavirus immunization in Israel

“…Our findings together with others' 21,22,[32][33][34] suggest that norovirus is a leading cause of gastroenteritis associated with seeking medical care and hospitalizations in young children, regardless of the introduction of the universal rotavirus immunization program. Despite the challenges facing the development of a norovirus vaccine, 23 prevention of norovirus gastroenteritis through vaccination is especially attractive in view of the success of rotavirus immunization in preventing rotavirus gastroenteritis and child mortality due to diarrheal diseases globally. 35 Currently, several norovirus vaccines are in development, 23,24,36,37 including a bivalent GI.1/GII.4 vaccines based on virus-like particles (VLPs) given intramuscularly and an oral vaccine based on non-replicating adenovirus vector expressing VP1 gene from GI.1 norovirus, 37 which have already been tested in clinical trials.…”

“…Despite the challenges facing the development of a norovirus vaccine, 23 prevention of norovirus gastroenteritis through vaccination is especially attractive in view of the success of rotavirus immunization in preventing rotavirus gastroenteritis and child mortality due to diarrheal diseases globally. 35 Currently, several norovirus vaccines are in development, 23,24,36,37 including a bivalent GI.1/GII.4 vaccines based on virus-like particles (VLPs) given intramuscularly and an oral vaccine based on non-replicating adenovirus vector expressing VP1 gene from GI.1 norovirus, 37 which have already been tested in clinical trials. Most (83%) norovirus positive patients in our study were children aged less than 18 months, about 40% were infants aged 6-11 months, in agreement with previous reports.…”

“…6 However such differences were not noted in other countries. 21,22 Given advances in the development of norovirus vaccines, 23,24 understanding the epidemiological characteristics of norovirus gastroenteritis becomes an important public health need. The study aim was to examine the incidence and characteristics of norovirus gastroenteritis among children in Israel.…”

Microbiological safety of ready‐to‐eat foods in low‐ and middle‐income countries: A comprehensive 10‐year (2009 to 2018) review

“…Notwithstanding, rotavirus vaccines are not yet widely available in some LMICs (Motayo, Faneye, & Adeniji, ; Sindhu, Babji, & Ganesan, ). Contrary to the case of rotavirus, development of norovirus vaccines is still ongoing (Hallowell, Parashar, & Hall, ; Riddle, Chen, Kirkwood, & MacLennan, ), and thus a licensed norovirus vaccine is currently unavailable (Huys, Grau, & Karst, ). Taken together, indications are that these two viruses and other foodborne viruses could continually pose a threat to RTE consumers in LMICs.…”

Enteric Viral Co-Infections: Pathogenesis and Perspective

“…Though less widely appreciated as a cause of AGE, sapovirus (SaV) is another member of the Caliciviridae family that causes diarrheal illness similar to NoV, especially in young children and the elderly, and frequently closely follows NoV in prevalence [ 42 , 43 ]. Although there are several NoV vaccines in development and two in clinical trials (bivalent GI.1/GII.4 vaccine and monovalent GI.1 oral vaccine) [ 44 , 45 ], there are no licensed vaccines against NoV or SaV.…”