Our assessment for the presence of neutralizing antibodies for hepatitis C virus (HCV) in an experimental intravenous immune globulin (HCIGIV) preparation enriched in anti-HCV including antibodies to HCV envelope glycoproteins, E1 and E2, in chimpanzees is about to be completed. HCIGIV prepared from about 200 anti-HCV positive donors was able to neutralize a low-titer inoculum, 64 chimpanzee infectious dose (CID50) of HCV-H inoculum while a commercial IGIV lot (devoid of both anti-E1 and anti-E2 when assayed) produced from anti-HCV screened plasma was not. The experimental chimpanzee exhibited neither elevated ALT nor detectable HCV RNA over a period of 58 weeks; passive anti-HCV was present until week 23. To check the susceptiblity of the experimental chimpanzee, it was challenged at week 59 with the same HCV-H inoculum at 64 CID50. HCV RNA again was detectable within one week of challenge, and reach high levels at both weeks 63 and 64, thereby demonstrating susceptibility. Thus, we can conclude that neutralizing antibodies to HCV are produced by infected individuals and that a high titered anti-HCV immunoglobulin preparation might be useful for the prophylaxis of HCV infections. However, anti-HCV was also detectable within one week of challenge suggesting that this was an anamnestic response and that cellular immunity may be involved. The finding requires further investigation. We were one of the 16 testing laboratories participated in a collaborative study organized by NIBSC/CLB to perform anti-HAV assays so to calibrate a replacement standard for the International Standard for hepatitis A immunoglobulin. The reason for the need for such replacement was because we informed both WHO and CLB that the current WHO standard which was established in late 1970s by CBER and subsequently provided to WHO contained HCV RNA. We continued to assess the levels of anti-HAV in IG made by 4 manufacturers and IGIV made by 6 manufacturers. IG is indicated for the prophylaxis of HAV and thereby it is crucial to measure the containing anti-HAV. The current WHO/CBER anti-HAV Standard (albeit HCV RNA being positive) which, when reconstituted, contains 100 IU/mL was used as a potency reference. Although more current lots of IG and IGIV need to be assayed and the statistical analysis from the interim data has yet to be carried out, preliminary results appear to indicate that the anti-HAV levels were higher in products derived from Source Plasma than those from recovered plasma.
