Norwalk Virus Vaccines: Challenges and Progress

Abstract

Human caliciviruses (HuCVs) are the major cause of outbreaks of acute nonbacterial gastroenteritis throughout the world. An increasing recognition of the clinical significance of these viruses as human pathogens causing foodborne and waterborne disease indicates that an effective vaccine would be useful. This article reviews the current challenges that exist for the development of a vaccine for the HuCVs as well as the status of development of a candidate vaccine. HuCVs are viruses that exhibit a restricted tropism for infection of the gastrointestinal tract of humans, and a volunteer model of infection and disease is available. As pathogens with a restricted host range, the HuCVs are excellent models for understanding the mechanisms that mediate and regulate viral infection of the gastrointestinal tract and mucosal immunity in humans.

Systemic, Mucosal, and Heterotypic Immune Induction in Mice Inoculated with Venezuelan Equine Encephalitis Replicons Expressing Norwalk Virus-Like Particles

“…Because NLVs are mucosal pathogens, it is likely that the ability to induce IgA responses at mucosal surfaces will be a necessary feature of an effective NLV vaccine (18). Therefore, we examined whether subcutaneous inoculation with VRP-NV1 results in the production of antigen-specific mucosal IgA.…”

“…In developing countries, the overall extent of NLVassociated disease burden remains to be resolved, but infection can lead to malnutrition in young children and infants (53,55). An effective vaccine would be useful for health care providers, food handlers, military personnel, and other at-risk populations to prevent the significant morbidity and potential mortality associated with NLV infection (18,45,63).…”

“…While these oral vaccine strategies mimic the natural route of NLV infection, serum and mucosal immune responses to Norwalk virus capsid proteins are modest and below the levels exhibited after wild-type Norwalk virus infection (18,45,63).…”

An Intranasally Delivered Toll-Like Receptor 7 Agonist Elicits Robust Systemic and Mucosal Responses to Norwalk Virus-Like Particles

“…Norwalk virus (NV), the prototype virus of the genus Norovirus, is a major cause of nonbacterial gastroenteritis in humans (12). Annually, noroviruses cause an estimated 21 million infections in the United States and 200 thousand deaths among children in developing countries (40).…”

Recombinant Norwalk Virus-Like Particles Administered Intranasally to Mice Induce Systemic and Mucosal (Fecal and Vaginal) Immune Responses

“…Outbreaks frequently occur in day care centers, schools, nursing homes, hospitals, and the military. The increasing clinical significance of these infections suggests that an effective vaccine could be useful (16).…”