LA JOLLA, Calif.—One of the main challenges of developing vaccines against viral infections like hepatitis C is virus variability. Recently, researchers at The Scripps Research Institute and other facilities attempted to develop broadly neutralizing antibodies that help the body fend off infection by delaying the process long enough for the body to muster its natural defenses. They reported their efforts in Nature Medicine.
Using a phage display library, the researchers initially identified 115 clones that showed specific binding to the HCV E2 glycoprotein representing 36 distinct Fabs. They converted seven Fabs into full length IgG1s and noted that the resulting mAbs bound different genotype HCVs with nanomolar affinity. The scientists then tested the neutralizing ability of the mAbs. They found that antibodies that bound E2 in an ELISA did not necessarily neutralize virus, and that only antigenic region 3 (AR3)-specific antibodies bound both genotypes tested and could cross-neutralize different viral strains.
The researchers tested the antibodies in a human liver-chimeric mouse model to determine whether the antibodies can protect against HCV challenge. They administered the antibodies intraperitoneally and then infected the mice with HCV, assessing viral load up to 6 weeks post-inoculation. In mice receiving AR3 mAbs, HCV was cleared 6 days after challenge and 6 weeks after inoculation, 40-75% of the mice receiving AR3 mAbs were still protected.
The present inoculations require high concentrations of mAbs, so a lot of work still has to be done to improve the potency of the immunotherapy, but the researchers feel these results bode well for future vaccine efforts.