Hepatitis C cross-genotype immunity and implications for vaccine development.
View / Open Files
Authors
Krajden, Mel
Shoveller, Jean
Gustafson, Paul
Gilbert, Mark
Wong, Jason
Tyndall, Mark W
Janjua, Naveed Zafar
The BC-HTC Team
Publication Date
2017-09-26Journal Title
Sci Rep
ISSN
2045-2322
Publisher
Springer Science and Business Media LLC
Volume
7
Issue
1
Pages
12326
Language
eng
Type
Article
Physical Medium
Electronic
Metadata
Show full item recordCitation
Islam, N., Krajden, M., Shoveller, J., Gustafson, P., Gilbert, M., Wong, J., Tyndall, M. W., et al. (2017). Hepatitis C cross-genotype immunity and implications for vaccine development.. Sci Rep, 7 (1), 12326. https://doi.org/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.
Keywords
The BC-HTC Team, Humans, Hepacivirus, Hepatitis C, Viral Envelope Proteins, Viral Hepatitis Vaccines, Hepatitis C Antibodies, Treatment Outcome, Immunization, Secondary, Vaccination, Cohort Studies, Genotype, Adult, Middle Aged, Female, Male, Cross Protection, Antibodies, Neutralizing
Identifiers
External DOI: https://doi.org/10.1038/s41598-017-10190-8
This record's URL: https://www.repository.cam.ac.uk/handle/1810/279654
Rights
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.