Influenza virus is a cause of substantial annual morbidity and mortality worldwide. Potential for theemergence of a new pandemic strain, through natural reassortment or via specific human design, withor without bioterrorist intent, is an ongoing concern. The most effective means of preventing influenzainfection is acquired immunity, derived from either prior infection or vaccination. In this application wepropose to study the B cell response to influenza with the purpose of better characterizing theresponse in children versus adults to inactive parenteral versus live mucosal immunization.
Aim 1 -Toquantify and characterize the memory and effector B cell response to wild type influenza infection, liveattenuated influenza vaccination and parenteral vaccination in children and adults and to correlatethese responses with antibody responses and with protection from infection. The magnitude andkinetics of B cell responses to influenza infection and vaccination will be measured and correlated withboth serum and mucosal humoral responses. It is our hypothesis that respiratory tract infection (vianatural infection or live attenuated virus immunization) will generate a larger effector and memory B cellresponse than parenteral vaccination with a non-replicating antigen.
Aim 2 - To characterize the breadthof heterosubtypic specificity of the humoral response in serum and at the B cell level following naturalinfection, five virus immunization and parenteral immunization. It is our hypothesis that infection (eitherwild type infection or live virus vaccination) induces a humoral response with greater heterosubtypicdiversity than parenteral immunization, and that this diversity will be apparent in serum and at the B cellclonal level when studied using monoclonal antibodies derived from responders to live versusinactivated vaccination.
Aim 3 -To identify and characterize the respiratory tract specific homingreceptor repertoire utilized by B cells to direct immune cells to the respiratory mucosa. It is ourhypothesis that respiratory tract specific lymphocyte trafficking occurs and that the signals mediatingthis trafficking can be identified by differential analysis of immune B cells (and T cells, see the resourcetechnical development project C on respiratory homing) induced following local versus systemicimmunization.
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