Taking cues from convalescence to improve vaccines against hepatitis C virus

Abstract

Hepatitis C virus (HCV) infection remains a worldwide public health issue despite direct-acting antivirals. A substantial proportion of infected individuals (15%-45%) spontaneously clear repeated HCV infections with genetically different viruses by generating broadly neutralizing antibodies (bNAbs). However, translating this response into an effective vaccine strategy has been unsuccessful. In this issue of the JCI, Frumento and colleagues report on their study of bNAb evolution longitudinally in convalescent individuals with repeated infections. Using pseudotyped viruses, well-characterized monoclonal antibodies, and complex modeling, the authors show that multiple exposures to antigenically related, antibody-sensitive viral envelope proteins induced potent bNAbs. This work provides valuable insight into the best strategies for developing HCV vaccines in the future that may successfully reproduce the immunity induced during natural exposures.

Figure 1. Characterization of the antibody response in HCV-infected patients.

Frumento et al. (13) studied four different patient populations longitudinally. The HCV antibody response was evaluated using an HCVpp assay in which serological samples were compared with reference antibodies (mAbs) that had known neutralizing epitopes. They also performed an ELISA with reference mAbs to quantify antibody binding to E1 and E2 proteins derived from certain patient populations. Further regression analysis, deconvolution analysis, and hierarchical clustering revealed that neutralization breadth and potency correlated with viremia duration, multiple distinct infections, and specific antibody-sensitive epitopes. Antigenically similar HCV strains may associate with increased neutralizing antibody potency and breadth.