Vaccine-induced cross-genotype reactive neutralizing antibodies against hepatitis C virus

Abstract

We detected cross-reactive neutralizing antibodies (NtAb) against hepatitis C virus (HCV) in chimpanzees vaccinated with HCV-1 (genotype 1a) recombinant E1/E2 envelope glycoproteins. Five vaccinated chimpanzees, protected following HCV-1 challenge, were initially studied using the heterologous H77 (genotype 1a) HCVpp assay. All animals had developed NtAb after the second vaccination; 4 animals had reciprocal titers of ≥200 at the time of challenge. Using genotypes 1a-6a HCV pseudoparticles (HCVpp) and cell culture-derived HCV (HCVcc) assays, cross-reactive NtAb were detected against 1a, 4a, 5a, and 6a, with limited reactivity against 2a and 3a. Our study provides encouragement for the development of a recombinant envelope-based vaccine against hepatitis C.

Figure 1.

Humoral immune responses in HCV-1 E1/E2-vaccinated chimpanzees. A, Vaccination with HCV-1 E1/E2 and challenge with HCV-1. B, Revaccination with HCV-1 E1/E2 and challenge with H77. The time of vaccinations is indicated by black arrows. The time of challenge is week 0. Qualitative detection of HCV RNA in reverse transcription–nested polymerase chain reaction is indicated (on top) by black (positive) and white (negative) rectangles. Black bars indicate NtAb detected in the HCVpp H77 assay (1:50 dilution tested). Percentage of neutralization was calculated by comparison with serum from a naive animal. Ch653 was not included for analysis of serial samples because it had low HCVpp NtAb titers at the day of challenge.