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 1,200 children daily worldwide, principally in developing countries. Taking into account that the epidemiology of rotavirus induced disease and the response to rotavirus vaccines has been different in developed and less developed countries it is critical that studies aimed at understanding the immune response against RV be studied in both settings. This research is the renewal of FIRCA grant TWO5647-03, and will be done primarily in Colombia, South America at the Instituto de Genetica Humana of the Pontificia Universidad Javeriana in collaboration with Manuel Franco and Juanita Angel as an extension of NIH Grant # R37 AI21362 (Harry Greenberg, PI). Our current FIRCA grant deals with the study of IgD- virus specific B cells (mostly isotype switched IgA and IgG cells) induced during acute rotavirus infection. The major objective of the renewal is to extend these studies to the study of long term isotype switched (IgD-) and non isotype switched (IgD+/-) memory B cells that are present at low frequencies following acute infection and are responsible for long term immunity. For this purpose we will use a flow cytometry assay and a complimentary limiting dilution assay to identify RV specific memory B cells. A practical long-term goal of this project is to find parameters that correlate with protection induced by rotavirus vaccines. We hypothesize that circulating RV specific memory B cells are the most easily measured and most direct correlate of protection against RV disease. Since rotaviruses replicate primarily in the intestinal mucosa, another long-term goal of this proposal is to gain a better understanding of the general nature of the memory immune response to rotavirus in particular, as well as a deeper understanding of the memory humoral mucosal immune response in general.

National Institute of Health (NIH)
Fogarty International Center (FIC)
Small Research Grants (R03)
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International and Cooperative Projects 1 Study Section (ICP)
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Sina, Barbara J
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Stanford University
Schools of Medicine
United States
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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