Hepatitis C cross-genotype immunity and implications for vaccine development

Nazrul Islam,Maria Alvarez,Mark Gilbert,Hasina Samji,Mark W Tyndall,Amanda Yu,Mei Chong,Zahid A Butt,Jean Shoveller,Margot Kuo,Seyed Ali Mussavi Rizi,Jason Wong,Mel Krajden,Nabin Shrestha,Naveed Zafar Janjua,Paul Gustafson

doi:10.1038/s41598-017-10190-8

Abstract

While about a quarter of individuals clear their primary hepatitis C (HCV) infections spontaneously, clearance (spontaneous or treatment-induced) does not confer sterilizing immunity against a future infection. Since successful treatment does not prevent future infections either, an effective vaccine is highly desirable in preventing HCV (re)infection. However, development of an effective vaccine has been complicated by the diversity of HCV genotypes, and complexities in HCV immunological responses. Smaller studies on humans and chimpanzees reported seemingly opposing results regarding cross-neutralizing antibodies. We report a lack of cross-genotype immunity in the largest cohort of people to date. In the adjusted Cox proportional hazards model, reinfection with a heterologous HCV genotype (adjusted Hazard Ratio [aHR]: 0.45, 95% CI: 0.25–0.84) was associated with a 55% lower likelihood of re-clearance. Among those who cleared their first infection spontaneously, the likelihood of re-clearance was 49% lower (aHR: 0.51, 95% CI: 0.27–0.94) when reinfected with a heterologous HCV genotype. These findings indicate that immunity against a particular HCV genotype does not offer expanded immunity to protect against subsequent infections with a different HCV genotype. A prophylactic HCV vaccine boosted with multiple HCV genotype may offer a broader and more effective protection.

Highlights

Ability to clear an episode of hepatitis C virus (HCV) infection, spontaneously[1,2] or after a successful treatment, does not protect against a future infection[3,4,5,6,7,8,9,10,11]
Study participants were observed for a median of 24.0 (IQR: 9.2–56.5) months to examine the spontaneous clearance of first infection, and 34.4 (IQR: 16.2–61.8) months to develop reinfection before entering the current study
We showed that reinfection with a heterologous HCV genotype was associated with a significant reduction in the likelihood of re-clearance among those who cleared their first HCV episode spontaneously indicating a lack of cross-genotype protective immune response against subsequent infections

Summary

Introduction

Ability to clear an episode of hepatitis C virus (HCV) infection, spontaneously[1,2] or after a successful treatment, does not protect against a future infection[3,4,5,6,7,8,9,10,11]. Some animal data reported cross-genotype immunity[15], while other findings suggested limited protection against heterologous HCV viral strains[16,19]. While these findings are important in understanding the natural history of HCV to lend support to vaccine development, these, and other epidemiological studies[7,17,18,20,21] had very small sample size that may have compromised their generalizability and their ability to examine factors determining the outcome following HCV reinfection. We examined if reinfection with a heterologous HCV genotype had any impact on re-clearance

Methods

Results

Discussion

Conclusion