Prospective studies demonstrated that viral clearance in acute HCV infection did not correlate with the development of neutralizing antibodies in chimpanzees.15, 22 In our study, CH10274 seroconverted and developed neutralizing antibodies against the homologous rechallenge
strain (JFH-1, genotype 2a) and a heterologous strain (genotype 1a), indicating the production of genotype crossreactive antibodies. However, LY2157299 mouse such antibodies were not able to prevent reinfection with the H77 strain. Thus, neutralizing antibodies may be capable of preventing low-level subclinical infection, such as the JFH-1cc infection,16 but they are not sufficient to control a robust high-viremic infection like the H77 infection.18 Following challenge with H77 virus in CH10274 and CH10273, we observed two distinct clinical courses. CH10273 had what appeared to be protective immunity because no viremia was detected. By contrast, CH10274 was infected with a fluctuating course of
viremia and viral clearance almost a year later. In humans, chronic HCV infection is characterized by selleckchem a 1-2 log decrease in viral load followed by a viral load stabilization in most cases of persistent infection within several months. However, fluctuating viremia in both patients with resolution of learn more infection and those with chronic infection
including intermittent negative HCV RNA test results after initial viremia have been observed. Furthermore, although most patients with an acute and self-limited course of HCV infection clear infection within 6 months, viral clearance has been also reported 1 and 2 years after diagnosis of acute infection.23 As discussed above, although CH10274 possessed antibodies with neutralizing activity against the rechallenging viral strain, the antibodies appeared insufficient to prevent reinfection. We did not observe any significant level of neutralizing antibodies in CH10273 following heterologous challenge, suggesting that the observed sterilizing immunity was not associated with the development of neutralizing antibodies. Although both animals demonstrated HCV-specific T-cell responses in the blood, the magnitude of the HCV-specific T-cell response was higher in CH10274, who became reinfected. Because there is an ongoing redistribution and migration of T cells between blood, lymph nodes, and liver, we examined the intrahepatic immune response in both animals. Compared to other organs, the liver is particularly enriched with cells of the innate immune system, including natural killer (NK), natural killer T (NKT) cells, Kupffer cells (KC), DCs, and T cells, which participate in adaptive immune responses.