Dr. Jianrong Li speaks about the future of human norovirus vaccines
June 13, 2012 --
Last week, the Emerging Pathogen Institute’s Global Pathogens Laboratory had the privilege of hosting Dr. Jianrong Li of The Ohio State University. During his visit to The University of Florida, Dr. Li delivered a powerful, optimistic seminar titled “New Interventions against Human Norovirus: Progress, Opportunities, and Challenges.”
Human norovirus is a single-stranded positive-sense RNA virus of the family Caliciviridae responsible for more than 90% of nonbacterial gastroenteritis (stomach illness) worldwide and 60% of foodborne illness of a total 23 million cases in the United State every year. The primary difficulty in human norovirus research is the virus’s inability to be grown in cell culture and the lack of a small animal model for pathogenesis study, which severely hampers research efforts to generate a vaccine.
To counter this, Dr. Li’s group constructed a recombinant vesicular stomatitis virus (VSV) to express VP1, the major capsid protein of human norovirus. This modified virus, called rVSV-VP1, was attenuated (or weakened) in cell culture and mice models. Mammalian cells infected by rVSV-VP1 produced a high level of virus-like particles (VLPs) that are structurally and antigenically similar to native human norovirus. Mice vaccinated with this recombinant virus caused the norovirus capsid particles to grow continuously in animals, triggering high level of norovirus-specific humoral, cellular, and mucosal immune responses. Regrettably, as mice aren’t susceptible to human norovirus, the protective capability of rVSV-VP1 against actual human norovirus cannot be examined in these models.
To overcome this challenge, Dr. Li’s group developed a Gnotobiotic pig challenge model to examine the pathogenesis of human norovirus and to test the immunogenicity of the rVSV-VP1 vaccine, in which Gnotobiotic pigs were vaccinated with rVSV-VP1.This not only induced high levels of norovirus-specific immunity, but also protected from norovirus-induced gastroenteritis, viral shedding in feces (a major cause of secondary transmissions), and pathological lesions in the intestines.
These observations demonstrated that VSV-based human norovirus vaccine triggered strong immunity in swine and protected gnotobiotic pigs against human norovirus. Based on this evidence, it can be concluded that VSV-based vaccine is a promising live candidate vaccine against human norovirus.