The primary objective of Project 2 is to expand on our studies of humoral immune response to acute hepatitis C virus (HCV) infection by examining the clinical and molecular correlates of potent neutralizing antibody responses. We have recently demonstrated that anti-HCV neutralizing antibodies drive the evolution of HCV proteins E1 and E2 during acute infection, indicating that neutralizing antibodies detected in an in vitro assay are capable of reducing viral fitness in vivo. In addition, available evidence from acute Infections indicates that high-titer neutralizing antibody responses are present in persons who go on to clear viremia, and not in those who progress to chronicity. We hypothesize that neutralizing antibodies are a predictive marker of clearance of acute HCV infection, and that evasion of these responses is a constrained mechanism for viral persistence. Thus, we propose the following aims to elucidate the clinical utility and basic mechanisms of HCV neutralization: (I) To define the positive predictive value of a potent anti-HCV neutralizing antibody response as a predictor of clearance during acute infection, and (II) To investigate the mechanisms by which HCV evades neutralizing antibody responses during acute infection. Results of studies of cellular immune responses from Project 1 will be integrated to expand knowledge of the interplay between humoral and cellular immune responses to HCV in humans. We have already demonstrated that we can obtain the critical specimens required for this investigation and will be able to conduct unique longitudinal studies of adaptive immune responses in persons transitioning from acute to established infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI088791-04
Application #
8445242
Study Section
Special Emphasis Panel (ZAI1-BP-M)
Project Start
Project End
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
4
Fiscal Year
2013
Total Cost
$302,632
Indirect Cost
$161,374
Name
Johns Hopkins University
Department
Type
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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