Rapid and sustained autologous neutralizing response leading to early spontaneous recovery after HCV infection

After HCV infection, the association between the humoral response and viral sequence evolution remains unclear. We investigated the mechanisms leading to early HCV clearance and spontaneous recovery in two patients. The early evolution of the HCV envelope glycoproteins, and the infectivity spectrum of variants were explored using retroviral pseudoparticles bearing HCV envelopes. Ability of the autologous neutralizing response to control these variants was analyzed. For the first case, the maximum neutralizing activity was for serum collected between two and three months post ALT peak, this activity was still detectable after 30 months. For the second case, autologous neutralizing activity against the variant isolated at the ALT peak was detected in every serum collected between 4 days and 13 months after. The neutralizing response was sustained beyond the time at which the virus was cleared. This raise interesting questions about the role of such antibodies in case of re-exposure.