The use of DNA for immunizations represents a new approach to raising immune responses. In this continuation, studies are proposed to (i) study the role of professional antigen presenting cells in the initiation of DNA-raised responses, (ii) to define parameters that determine whether a DNA-raised response will be biased towards Th1 or Th2 T-cell help, (iii) to study the role of germinal centers in DNA raised antibody responses, (iv) to characterize the cytolytic T-cells (CTL) raised by """"""""Th1"""""""" and """"""""Th2"""""""" DNA immunizations, and (v) to study the consequences of different types of DNA-raised T-help for challenge infections. Studies on antibody and antibody-mediated protection will use DNAs expressing normal (membrane-bound) and secreted forms of the influenza H1 hemagglutinin glycoprotein and the A/PR/8/34 (H1N1) murine influenza virus model. Studies on CTL and CTL-mediated protection will use DNA expressing the LCMV nucleoprotein (NP) and LCMV infections of mice. Antigen presenting cells will be examined in draining lymphoid tissue using DNA-expressed green fluorescent protein and in vitro restimulation of H1-specific Th cell lines. Co-transfected lymphokines, lymphokine knock out mice, and lymphokine neutralizing antibodies will be used to analyze the dependence on lymphokines of the Th-biases of DNA raised responses. DNA immunizations of germinal center knockout (CD40 knock out) and intact mice will be used to study the differentiation and function of Th cells and B cells that do, and do not enter the germinal center reaction. Studies on CTL will test for differences in frequency and function of CD8+ cells raised by Th1 and Th2-biased DNA immunizations. Post challenge studies will examine the effects of Th1- and Th2-biased responses on the control of infection and post challenge immunopathology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI034946-08
Application #
6170287
Study Section
Virology Study Section (VR)
Program Officer
Lambert, Linda C
Project Start
1994-01-01
Project End
2002-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
8
Fiscal Year
2000
Total Cost
$333,145
Indirect Cost
Name
Emory University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
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Boyle, C M; Robinson, H L (2000) Basic mechanisms of DNA-raised antibody responses to intramuscular and gene gun immunizations. DNA Cell Biol 19:157-65
Ross, T M; Xu, Y; Bright, R A et al. (2000) C3d enhancement of antibodies to hemagglutinin accelerates protection against influenza virus challenge. Nat Immunol 1:127-31

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