Meta-Analysis of Hepatitis C Virus Vaccine Efficacy in Chimpanzees Indicates an Importance for Structural Proteins

Background & Aims

Studies in patients and chimpanzees that spontaneously cleared hepatitis C virus (HCV) infections demonstrated that natural immunity to the virus is induced during primary infections and that this immunity can be cross protective. These discoveries led to optimism about prophylactic HCV vaccines, and several studies were performed in chimpanzees, although most included fewer than 6 animals. To draw meaningful conclusions about the efficacy of HCV vaccines in chimpanzees, we performed statistical analyses of data from previously published studies from different groups.

Methods

We performed a meta-analysis that compared parameters among naïve (n = 63), vaccinated (n = 53), and rechallenged (n = 36) animals, including peak RNA titer postchallenge, time points of peak RNA titer, duration of viremia, and proportion of persistent infections.

Results

Each vaccination study induced immune responses that were effective in rapidly controlling HCV replication. Levels of induced T-cell responses did not indicate vaccine success. There was no reduction in the rate of HCV persistence in vaccinated animals, compared with naïve animals, when nonstructural proteins were included in the vaccine. Vaccines that contained only structural proteins had clearance rates that were significantly higher than vaccines that contained nonstructural components (P = .015).

Conclusions

The inclusion of nonstructural proteins in HCV vaccines might be detrimental to protective immune responses, and/or structural proteins might activate T-cell responses that mediate viral clearance.

Keywords: Correlates of Protection, Viral Kinetics, ELISPOT Responses

Abbreviations used in this paper: ELISPOT, enzyme-linked immunospot, GT, genotype, HCV, hepatitis C virus, HIV, human immunodeficiency virus, IQR, interquartile range, NS, nonstructural, NTR, nontranslated region, RdRp, RNA-dependent RNA polymerase