Mosa, Alexander I, Campo, David S, Khudyakov, Yury, AbouHaidar, Mounir G, Gehring, Adam J, Zahoor, Atif, Ball, Jonathan K, Urbanowicz, Richard A 
ORCID: 0000-0002-2461-4993 and Feld, Jordan J
(2023)
Polyvalent immunization elicits a synergistic broadly neutralizing immune response to hypervariable region 1 variants of hepatitis C virus.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 120 (24).
e2220294120-.
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Mosa et al 2023.pdf - Author Accepted Manuscript Download (2MB) | Preview |
Abstract
A hepatitis C virus (HCV) vaccine is urgently needed. Vaccine development has been hindered by HCV's genetic diversity, particularly within the immunodominant hypervariable region 1 (HVR1). Here, we developed a strategy to elicit broadly neutralizing antibodies to HVR1, which had previously been considered infeasible. We first applied a unique information theory-based measure of genetic distance to evaluate phenotypic relatedness between HVR1 variants. These distances were used to model the structure of HVR1's sequence space, which was found to have five major clusters. Variants from each cluster were used to immunize mice individually, and as a pentavalent mixture. Sera obtained following immunization neutralized every variant in a diverse HCVpp panel (n = 10), including those resistant to monovalent immunization, and at higher mean titers (1/ID<sub>50</sub> = 435) than a glycoprotein E2 (1/ID<sub>50</sub> = 205) vaccine. This synergistic immune response offers a unique approach to overcoming antigenic variability and may be applicable to other highly mutable viruses.
| Item Type: | Article |
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| Uncontrolled Keywords: | hepatitis c virus, vaccine, HVR1 |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 26 Jul 2023 13:02 |
| Last Modified: | 05 Dec 2023 02:30 |
| DOI: | 10.1073/pnas.2220294120 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3171920 |
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