Project 3: Complement receptors in humoral immunity to influenza. P.I. Michael C. Carroll Abstract: Influenza virus represents a major worldwide health problem. Of the 3 known strains, influenza A is probably the best studied as it infects not only humans but other mammals and can be adapted to animal models. The major antigenic targets-hemagglutinin and neuraminidase- undergo structural changes such that antibodies formed against one strain generally are not protective with a related strain. Because of this """"""""antigenic variation"""""""", neutralizing antibodies which are normally protective are not long lasting and necessitate annual vaccination. In addition, B cell memory responses are generally targeted to a few dominant epitopes. Vaccines that enhance humoral immunity to a broader range of epitopes and especially to the conserved regions of the outer coat proteins are less likely to be affected by antigenic variation. The complement system participates in both the innate and adaptive response to influenza. A major role for complement in humoral immunity is mediated via its receptors CD21 and CD35 that are expressed on both B cells and follicular dendritic cells. Understanding how complement receptors enhance persistent antibody to influenza and the B cell memory response could provide insight into design of novel vaccines that would help overcome susceptibility to antigenic variation of the virus. In order to further our understanding of the role of complement receptors in humoral immunity to influenza and to test the efficacy of complement C3d as a molecular adjuvant two aims are proposed:
Aim 1 : Test the hypothesis that complement receptors CD21/CD35 are critical for an effective humoral response to influenza.
Aim 2 : Identify the mechanism for uptake and transport of influenza virus into peripheral lymph node follicles.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI078897-02
Application #
7901518
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
2
Fiscal Year
2009
Total Cost
$577,345
Indirect Cost
Name
Harvard University
Department
Type
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
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