Immunity in Hepatitis C Infection

Abstract

Polymerase chain reaction (PCR) and newer serologic assays for hepatitis C virus (HCV) were used to investigate 19 HCV cross-challenge episodes in chimpanzees. In these cross-challenges, 59% showed seroconversion after challenge, 33% showed reappearance of HCV-associated hepatocellular ultrastructural changes, 5 animals not PCR-positive at the time of challenge showed return of PCR positivity, and 26% developed hepatitis after rechallenge. A total of 74% showed at least one of these signs of reinfection. The frequency of development of serologic and ultrastructural responses was, however, reduced in secondary compared with primary infections (P less than .01). In 10 animals, the cross-challenge was done with heterologous strains, and in 9 with the originally infecting virus. There was no significant difference in the responses to homologous and heterologous challenges. The data suggest relatively weak immunity in HCV infections.

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

“…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 during HCV infection. 5,19 A multispecific cytotoxic T lymphocyte (CTL) response may control HCV replication to some extent, yet the cellular immune response appears to be incapable of clearing the virus in most individuals.…”

“…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.…”

Modulation of immune responses to hepatitis C virus envelope E2 protein following injection of plasmid DNA using single or combined delivery routes

“…However, various clinical and experimental studies realized in humans and chimpanzees have suggested that frequently protective immunity is not developed following primary infection, a factor that could result in reinfection of patients or animals when exposed to new challenges. [9][10][11] There are two candidate antigens susceptible to induce protective (neutralizing) antibodies: the viral envelope glycoproteins, E1 and E2. Immunization of chimpanzees with recombinant E1 and E2 proteins has been shown to induce protection against a homologous challenge supposedly via the induction of neutralizing antibodies.…”

Hepatitis C virus quasispecies in HIV-infected women: Role of injecting drug use and highly active antiretroviral therapy (HAART)

“…It was demonstrated in chimpanzees that the presence of persistent infection does not provide protection against subsequent infection with heterologous and even with homologous strains. [56][57][58] As the neutralizing antibodies are isolate-specific, they may be ineffective against other variants present in the complex of quasispecies: in a chimpanzee challenge experiment a hyperimmune anti-HVR1 serum raised against the predominant strain present in the inoculum was able to neutralize the predominant clone but was ineffective against minor variants. 59 However, there is clear evidence for the presence of some crossreactive immunity as convalescent chimpanzees and humans usually do not develop chronic infection upon reexposure.…”