Scientific Publications by FDA Staff

Proc Natl Acad Sci U S A 2004 Jul 6;101(27):10149-54

Neutralizing antibody response during acute and chronic hepatitis C virus infection.

Logvinoff C, Major ME, Oldach D, Heyward S, Talal A, Balfe P, Feinstone SM, Alter H, Rice CM, McKeating JA

McKeating JA, Rockefeller Univ, Ctr Study Hepatitis C, 1230 York Ave, New York, NY 10021 USA Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA US FDA, Lab Hepatitis Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA Cornell Univ, Weill Med Coll, Dept Med, New York, NY 10021 USA Cornell Univ, Weill Med Coll, Ctr Study Hepatitis C, New York, NY 10021 USA Columbia Univ, Div Infect Dis, New York, NY 10032 USA NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA

Little is known about the role of Abs in determining the outcome of hepatitis C virus (HCV) infection. By using infectious retroviral pseudotypes bearing HCV glycoproteins, we measured neutralizing Ab (nAb) responses during acute and chronic HCV infection. In seven acutely infected health care workers, only two developed a nAb response that failed to associate with viral clearance. In contrast, the majority of chronically infected patients had nAbs. To determine the kinetics of strain-specific and crossreactive nAb emergence, we studied patient H, the source of the prototype genotype 1a H77 HCV strain. An early weak nAb response, specific for the autologous virus, was detected at seroconversion. However, neutralization of heterologous viruses was detected only between 33 and 111 weeks of infection. We also examined the development of nAbs in 10 chimpanzees infected with H77 clonal virus. No nAb responses were detected in three animals that cleared virus, whereas strain-specific nAbs were detected in six of the seven chronically infected animals after approximately 50 weeks of infection. The delayed appearance of high titer crossreactive nAbs in chronically infected patients suggests that selective mechanism(s) may operate to prevent the appearance of these Abs during acute infection. The long-term persistence of these nAbs in chronically infected patients may regulate viral replication.