Rotaviruses (RVs) are the most important cause of severe dehydrating diarrhea in children in both developed and less developed countries. It is estimated that RV are responsible for the death of approximately 2000 children daily worldwide principally in developing countries. Studies in animals and in humans indicate that humoral immune mechanisms appear to be the primary determinants of protection from reinfection following wild-type disease or vaccination. Better methods are needed to characterize the qualitative and quantitative nature of the humoral immune response in children from developed and less developed countries. The proposed studies will be done primarily in Colombia- South America as an extension of NIH Grant: (R37 AI21362). Using B cell ELISPOTS and a novel flow cytometry assay we plan to quantify and study the phenotype of rotavirus specific B cells induced after natural rotavirus infection in children and adults in Colombia, and in children after natural rotavirus infection and after administration of a rotavirus vaccine. We will study these lymphocytes for the presence of molecules implicated in lymphocyte homing to the intestinal mucosa and B cell maturation markers that will aide in differentiating effector vs. memory B cells. A practical long-term goal of this project is to find parameters that correlate with protection induced by rotavirus vaccines. Since rotaviruses replicate almost exclusively in the intestinal mucosa, another long-term goal of this project is to gain a better understanding of the molecular determinants of the immune response to rotavirus in particular, as well as a deeper understanding of the humoral mucosal immune response in general with specific emphasis on B cell memory and homing.
| Narvaez, Carlos F; Feng, Ningguo; Vasquez, Camilo et al. (2012) Human rotavirus-specific IgM Memory B cells have differential cloning efficiencies and switch capacities and play a role in antiviral immunity in vivo. J Virol 86:10829-40 |
| Rojas, Olga Lucia; Narvaez, Carlos Fernando; Greenberg, Harry B et al. (2008) Characterization of rotavirus specific B cells and their relation with serological memory. Virology 380:234-42 |
| Franco, Manuel A; Angel, Juana; Greenberg, Harry B (2006) Immunity and correlates of protection for rotavirus vaccines. Vaccine 24:2718-31 |
| Gonzalez, Ana Maria; Jaimes, Maria C; Cajiao, Isabela et al. (2003) Rotavirus-specific B cells induced by recent infection in adults and children predominantly express the intestinal homing receptor alpha4beta7. Virology 305:93-105 |
