For mucosal vaccines to reach their full potential in disease prevention it is imperative that we understand the molecular mechanisms of IgA antibody secreting cell (ASC) homing to mucosal tissues. This is particularly true if vaccines are to be designed in which a vaccine is administered via one mucosal surface but where antibody protection is also desirable at other mucosal sites. The purpose of this study is to define differences in the adhesion molecule phenotype of IgA ASC accumulating in the small intestine and lactating mammary gland. The functional relevance of adhesion molecules will then be tested in vivo through the use of function blocking antibodies. The effect of function blocking antibodies on IgA ASC accumulation to mucosal tissues will be determined through ELISA and ELISPOT analysis. Through understanding differences in the molecular mechanisms of IgA ASC accumulation to these two tissues we will set the stage for understanding how ASC home to all mucosal sites. Understanding how cells accumulate in these sites is the first step to better targeting IgA mediated protection to diverse mucosal tissues following vaccination. Most pathogens enter the body through mucosal surfaces. The immune system is uniquely equipped to protect these surfaces through the production of IgA antibodies. We propose to study the mechanisms by which IgA antibody producing cells home to, and accumulate in, mucosal tissues. This knowledge will ultimately lead to the design of more effective mucosal vaccines ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15AI072769-01
Application #
7194931
Study Section
Special Emphasis Panel (ZRG1-F07-L (20))
Program Officer
Prograis, Lawrence J
Project Start
2007-03-15
Project End
2010-02-28
Budget Start
2007-03-15
Budget End
2010-02-28
Support Year
1
Fiscal Year
2007
Total Cost
$225,000
Indirect Cost
Name
Brigham Young University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
009094012
City
Provo
State
UT
Country
United States
Zip Code
84602
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Liu, Bin; Wilson, Eric (2010) The antimicrobial activity of CCL28 is dependent on C-terminal positively-charged amino acids. Eur J Immunol 40:186-96
Low, Elizabeth N; Zagieboylo, Lauren; Martino, Benjamin et al. (2010) IgA ASC accumulation to the lactating mammary gland is dependent on VCAM-1 and alpha4 integrins. Mol Immunol 47:1608-12
Morteau, Olivier; Gerard, Craig; Lu, Bao et al. (2008) An indispensable role for the chemokine receptor CCR10 in IgA antibody-secreting cell accumulation. J Immunol 181:6309-15