Hepatitis C cross-genotype immunity and implications for vaccine development

Hepatitis C cross-genotype immunity and implications for vaccine development
Nazrul Islam, Mel Krajden, Jean Shoveller, Paul Gustafson, Mark Gilbert, Jason Wong, Mark W. Tyndall, Naveed Zafar Janjua & The BC-HTC Team

Received:31 May 2017

Accepted:02 August 2017

Published online:26 September 2017

Full Text Available online @ Scientific Reports 

Scientific Reports 7, Article number: 12326 (2017)

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.

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