Objectives
Rotaviruses are the most
important cause of diarrhea in children under 5 years of age worldwide.
Because of this
early age of infection, vaccines, especially live oral vaccines, will
encounter the suppressive effects of maternal antibodies. Our aims are to
investigate the mechanism of maternal antibody suppression and the means to
overcome the immunosuppression. Both aims will be achieved by testing different vaccine
formulations, doses, routes of immunization and adjuvants in pigs with and
without experimentally administered circulating maternal antibodies
to human rotavirus (HRV).
In our laboratory we have established a neonatal gnotobiotic
pig model of rotavirus diarrhea using the Wa HRV strain, and have confirmed
the suppressive effects of maternal antibodies (in both serum and milk) on
mucosal and systemic immune responses and protection against experimental
challenge. Our goal is to clarify the mechanisms whereby maternal antibodies
suppress immune responses to viral antigens in neonates using live HRV and novel
virus-like particle vaccines. An understanding of these immunosuppressive
mechanisms and the means to overcome them will lead to more efficacious
vaccines for both RV and other pathogens infecting neonates.
