Identification of cross-reactive norovirus CD4+ T cell epitopes.

Immune responses and the components of protective immunity following norovirus infection in humans are poorly understood. Although antibody responses following norovirus infection have been partially characterized, T cell responses in humans remain largely undefined. In contrast, T cells have been shown to be essential for viral clearance of mouse norovirus (MNV) infection.

Viral shape-shifting: norovirus evasion of the human immune system.

Noroviruses are the most common cause of food-borne gastroenteritis worldwide, and explosive outbreaks frequently occur in community settings, where the virus can immobilize large numbers of infected individuals for 24-48 hours, making the development of effective vaccines and antiviral therapies a priority. However, several challenges have hampered therapeutic design, including: the limitations of cell culture and small-animal model systems; the complex effects of host pre-exposure histories; differential host susceptibility, which is correlated with blood group and secretor status; and the evolution of novel immune escape variants. In this Review, we discuss the molecular and structural mechanisms that facilitate the persistence of noroviruses in human populations.

Alphavirus-adjuvanted norovirus-like particle vaccines: heterologous, humoral, and mucosal immune responses protect against murine norovirus challenge.

The development of an effective norovirus vaccine likely requires the capacity to protect against infection with multiple norovirus strains. Advanced recombinant genetic systems and the recent discovery of a mouse-tropic norovirus strain (MNV) provide robust model systems for vaccine efficacy studies. We coadministered multivalent norovirus-like particle (VLP) vaccines with alphavirus adjuvant particles to mice and evaluated homotypic and heterotypic humoral and protective immunity to human and murine norovirus strains.

Immune mechanisms responsible for vaccination against and clearance of mucosal and lymphatic norovirus infection.

Two cardinal manifestations of viral immunity are efficient clearance of acute infection and the capacity to vaccinate against secondary viral exposure. For noroviruses, the contributions of T cells to viral clearance and vaccination have not been elucidated. We report here that both CD4 and CD8 T cells are required for efficient clearance of primary murine norovirus (MNV) infection from the intestine and intestinal lymph nodes.

Norovirus pathogenesis: mechanisms of persistence and immune evasion in human populations.

Noroviruses are important human pathogens known to cause epidemic outbreaks of severe gastroenteritis in communities, military barracks, cruise ships, hospitals, and assisted living communities, resulting in over 267,000,000 annual infections worldwide. Diversity within the norovirus genus allows this virus to persist in human populations, although a single genocluster, the GII.4 noroviruses, currently accounts for approximately 80% of all infections.

Antibody is critical for the clearance of murine norovirus infection.

Human noroviruses cause more than 90% of epidemic nonbacterial gastroenteritis. However, the role of B cells and antibody in the immune response to noroviruses is unclear. Previous studies have demonstrated that human norovirus specific antibody levels increase upon infection, but they may not be protective against infection.

Mechanisms of GII.4 norovirus persistence in human populations.

Background: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.

Multivalent norovirus vaccines induce strong mucosal and systemic blocking antibodies against multiple strains.

Noroviruses are important agents of human gastroenteritis characterized by extensive sequence variation in the major capsid structural protein that likely encodes critical antigenic determinants of protective immunity. The lack of an infection model has limited detailed characterizations of viral antigenic relationships and identification of the essential components for protective immunity. This information would contribute to efficacious vaccine design against a broad array of norovirus strains.