March 25, 2015
To anyone who has ever suffered from “the stomach flu,” take cheer – a vaccine may be on the near horizon.
Noroviruses produce an estimated 300 million cases a year worldwide of what is typically labeled “stomach flu.” Not only do the infections cause extreme discomfort and misery among their victims, noroviruses also contribute to roughly 260,000 deaths, mostly in low-income countries.
However, a new weapon in the battle against noroviruses may be on the horizon, according to a study from researchers at The University of North Carolina at Chapel Hill, in collaboration with Takeda Inc., a vaccine manufacturer.
The study, “Broad Blockade Antibody Responses in Human Volunteers Post-Immunization with a Multivalent Norovirus VLP Candidate Vaccine: Immunological Analyses from a Phase I Clinical Trial,” published online March 24 by PLOS Medicine, found that a multivalent candidate vaccine (a vaccine containing a mix of more than one norovirus strain) elicits broad antibody responses to a range of different norovirus strains, including strains not part of the vaccine or previously encountered by participants. These results indicate that a vaccine to norovirus may be available in the future.
The study was led by Lisa Lindesmith, MS, research specialist, and Ralph Baric, PhD, professor, both in the UNC Gillings School of Global Public Health’s Department of Epidemiology. Kari Debbink, PhD, and Jesica Swanstrom, BS, research specialist, both in epidemiology, and Martin Ferris, PhD, research assistant professor of genetics in the UNC School of Medicine, were among co-authors of the study.
“This study represents the best example of leveraging academic and industrial partnerships to achieve major breakthroughs in important global health problems effecting young children and the elderly,” Baric said.
Recent efforts to develop a norovirus vaccine have focused on virus-like particles (VLPs), which are constructed from molecules of the virus’s capsid (the virus’s outer protein shell). In a phase I clinical trial, one multivalent VLP vaccine elicited antibody generation, an indicator of a productive immune response, but it did not confer immunity to infection with different strains not included in the vaccine. In the current study, Lindesmith and colleagues characterized serum specimens from ten multivalent VLP vaccine clinical trial participants for antibodies to vaccine VLPs and also to VLPs representing viruses that were not contained in the vaccine.
The researchers found that this VLP vaccine strategy can elicit rapid antibody responses to a broad range of vaccine and non-vaccine VLPs, including to two VLPs representing human noroviruses that the study participants could not have encountered previously. Overall, antibodies to norovirus strains to which study participants had been exposed previously dominated the immune response.
These findings provide evidence that VLP-vaccine-induced norovirus immunity, if achieved, may overcome the capacity of noroviruses to evade immunity by antigenic drift, the gradual change of the antibody recognition sites on a pathogen over time.
These results must be interpreted cautiously. The study is small, and the assays used may not replicate the ways in which the immune system of a vaccine recipient will respond to true norovirus infection. Additionally, study participants were adults, 18 to 49 years old, while a vaccine is most needed for young children (who account for the majority of severe infections) and the elderly (who are most likely to die from infection). Next steps include further development of VLP-based vaccines and additional clinical trials.
“We have developed a new standard for the evaluation of vaccine performance that can be applied to many pathogens,” Lindesmith said. “These approaches tell us how to design better vaccines for vulnerable populations, including children and the elderly.”
The paper is available online.