Effect of Immune Globulin on the Prevention of Experimental Hepatitis C Virus Infection

Krawczynski, Krzysztof; Alter, Miriam J.; Tankersley, Donald L.; Beach, Michael J.; Robertson, Betty H.; Lambert, Stephen; Kuo, George; Spelbring, John; Meeks, Emory L.; Sinha, Saswati; Carson, D.

doi:10.1093/infdis/173.4.822

Cited by 176 publications

(99 citation statements)

References 26 publications

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“…Hepatitis B immunoglobulin prepared before the elimination of antibody to HCV ϩ blood donors appeared to protect French patients who underwent transplantation for HBV and HCV coinfection from recurrent HCV infection. 2,79 It was postulated that these immunoglobulin preparations contained large amounts of polyclonal HCV antienvelope antibodies, capable of neutralizing residual circulating HCV, thereby preventing HCV infection of the graft. Subsequent chimpanzee studies conducted at the Centers for Disease Control and Prevention have shown that a single dose of postexposure hepatitis C immunoglobulin (HCIG; prepared from HCV RNA ϩ donors) markedly prolonged the incubation period of acute HCV, whereas repeated doses reduced viremia levels in chronic infection.…”

Section: Posttransplantation Prophylaxismentioning

confidence: 99%

Treatment of recurrent hepatitis C

Gane

2002

Liver Transplantation

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Key Points 1. Treatment of established recurrent hepatitis C with interferon-␣ monotherapy does not achieve sustained virologic response (SVR). 2. Treatment of established recurrent hepatitis C with combination interferon plus ribavirin achieves SVR rates of 17% to 27%, but dropout rates approach 30%. 3. Pretransplant prophylaxis against recurrent hepatitis C with combination interferon plus ribavirin is poorly tolerated in patients with decompensated hepatitis C cirrhosis. 4. Posttransplant prophylaxis with combination interferon plus ribavirin prevents both recurrent viremia and hepatitis in 15% to 20% of patients, but dropout rates approach 50%. 5. Hepatitis C virus genotype is the best predictor of response to antiviral prophylaxis and treatment of recurrent hepatitis C. 6. Interferon-␣ therapy is not associated with an increased risk of allograft rejection in liver transplant recipients. 7. Ribavirin therapy is associated with increased hemolysis in liver transplant recipients. 8. Preliminary data suggest pegylated interferon monotherapy will have similar efficacy but better tolerability than combination interferon plus ribavirin. 9. In a recent study, posttransplant immunoprophylaxis with polyclonal hepatitis C immunoglobulin had no effect on recurrent viremia or hepatitis. (Liver Transpl 2002;8: S28-S37.)

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Section: Posttransplantation Prophylaxismentioning

confidence: 99%

Treatment of recurrent hepatitis C

Gane

2002

Liver Transplantation

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“…[5][6][7][8][9][10][11] Studies in chimpanzees have revealed that antibody neutralization of HCV is not easily attained. 12,13 Recently, Cooper et al observed that strong antibody responses to HCV proteins were not necessary for viral clearance in HCV-inoculated chimpanzees. 14 Several investigators have also observed that circulating HCV-specific antibodies do not prevent reinfection of chimpanzees with HCV.…”

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confidence: 99%

Protective immune response to hepatitis C virus in chimpanzees rechallenged following clearance of primary infection

et al. 2001

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Hepatitis C virus (HCV) infections were evaluated in chimpanzees that had previously cleared HCV and were rechallenged. Animals that had previously cleared HCV infection rapidly cleared homologous and heterologous virus upon rechallenge, indicative of a strong protective immunity. In one animal, sterilizing immunity was observed with regard to viremia, although viral RNA was transiently detected in the liver. Accelerated viral clearance following rechallenge with HCV was observed in animals that had not been exposed to HCV for over 16 Hepatitis C virus (HCV) infections represent a serious health problem. The majority of HCV infections develop into chronic infections that may progress to cirrhosis and hepatocellular carcinoma. 1 HCV is classified in the Hepacivirus genus of the Flaviviridae family. 2 The HCV genome is approximately 9.6 kb and consists of single-stranded RNA of positive polarity. The viral RNA has a single large open reading frame that encodes for a polyprotein of approximately 3,000 amino acids. 3 The structural proteins are located at the amino terminal end of the polyprotein and include the capsid protein and 2 envelope glycoproteins, E1 and E2. The nonstructural proteins are preceded by a p7 domain of unknown function and include NS2-NS5. The NS2 domain forms an autoprotease with the amino-terminal portion of NS3. The amino terminus of NS3 encodes a serine protease and the carboxy terminus encodes a helicase, which plays a role in viral RNA replication. NS4A is a cofactor for the serine protease. The viral RNAdependent RNA polymerase is encoded by NS5B. 4 The functions of NS4B and NS5A are unknown.The chimpanzee is the only animal model for studying HCV infection. Humans and chimpanzees with persistent HCV infections mount an antibody response to most HCV proteins. 5 HCV-specific antibody does not appear to protect humans and chimpanzees from infection and is actually associated with active viremia rather than viral clearance. The kinetics of antibody production to HCV proteins and the pattern of antibodies to individual proteins do not appear to predict disease outcome (clearance versus persistence).The humoral immune response to the nonstructural HCV proteins appears to be similar in humans and chimpanzees. 5 In contrast, antibody responses to HCV structural proteins are observed less frequently in chimpanzees than in humans for reasons not understood. [5][6][7][8][9][10][11] Studies in chimpanzees have revealed that antibody neutralization of HCV is not easily attained. 12,13 Recently, Cooper et al. observed that strong antibody responses to HCV proteins were not necessary for viral clearance in HCV-inoculated chimpanzees. 14 Several investigators have also observed that circulating HCV-specific antibodies do not prevent reinfection of chimpanzees with HCV. [15][16][17][18] Therefore, T cells may play a more critical role than antibodies in the resolution of HCV infection.HCV antigen-specific CD8 ϩ T cells have been observed in the peripheral blood and liver of humans and chimpanzees durin...

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“…In humans, it has been shown that nonspecific immunoglobulins (Igs) have some prophylactic effects on hepatitis C. [4][5][6] In chimpanzees, passive immunization with Ig preparations prolonged the incubation period of acute hepatitis C, and HCV infection was prevented after in vitro neutralization with plasma of a chronically infected patient. 7,8 Although it appears that the effects of passive immunization are limited and complete clearance of HCV is not usually accomplished, vaccination experiments have been more successful. When vaccinated with recombinant envelope proteins, chimpanzees developed high serum titers of anti-E2 protein (envelope-2 glycoprotein) antibodies and were protected from subsequent challenge with homologous isolates.…”

mentioning

confidence: 99%