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Journal of Virology, November 2004, p. 12252-12258, Vol. 78, No. 22
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.22.12252-12258.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Cellular Immune Responses in Seronegative Sexual Contacts of Acute Hepatitis C Patients

Sanaa M. Kamal,1,2,3* Ashraf Amin,2 Mohamed Madwar,2 Camilla S. Graham,1 Qi He,1 Ahmed Al Tawil,4 Jens Rasenack,3 Tatsunori Nakano,5,6 Betty Robertson,5 Alaa Ismail,2 and Margaret James Koziel1

Department of Infectious Diseases of Beth Israel Deaconess Medical Center and Harvard Medical School, Harvard Institutes of Medicine, Boston, Massachusetts,1 Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia,5 Department of Gastroenterology and Liver Diseases,2 Department of Pathology, Ain Shams Faculty of Medicine, Heliopolis, Cairo, Egypt,4 Department of Internal Medicine II, Gastroenterology and Hepatology, University of Freiburg, Freiburg, Germany,3 Department of Internal Medicine, Ichinomiya Nishi Hospital, Ichinomiya, Aichi, Japan6

Received 4 March 2004/ Accepted 14 June 2004

Acute hepatitis C virus (HCV) is typically defined as new viremia and antibody seroconversion. Rates and immunologic correlates of hepatitis C clearance have therefore been based on clearance of viremia only in individuals who initially had an antibody response. We sought to characterize the immunological correlates of clearance in patients with acute hepatitis C and their sexual contacts. We prospectively determined CD4+ and CD8+ cytotoxic T-lymphocyte responses in index patients with acute HCV and their sexual contacts who developed acute infection, either with or without spontaneous clearance, as well as those contacts who never developed viremia. Responses were measured using proliferation and ELISpot assays for CD4+ and CD8+ responses. We demonstrate in this prospective study that cellular immune responses can develop in exposed but persistently aviremic and antibody-negative individuals as well as those individuals with spontaneous clearance of acute HCV. These findings lend further credence to the importance of cellular immune responses in recovery from HCV and suggest that low exposure to HCV may lead to development of HCV-specific immune responses without ongoing HCV replication. This finding has important implications for HCV vaccine and therapeutic development.

* Corresponding author. Mailing address: Department of Infectious Diseases, Harvard Institutes of Medicine, 4 Blackfan Circle, Boston, MA 02115. Phone: (617) 784-6989. Fax: (617) 975-5235. E-mail: Sanaa.Kamal{at}link.net.

Journal of Virology, November 2004, p. 12252-12258, Vol. 78, No. 22
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.22.12252-12258.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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