Non-cognate ligands of hepatitis C virus envelope broadly neutralizing antibodies induce virus-neutralizing sera in mice

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F25%3A00638200" target="_blank" >RIV/86652036:_____/25:00638200 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15110/25:73633186 RIV/60461373:22330/25:43932760 RIV/00098892:_____/25:10159355

Result on the web

<a href="https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1624299/full" target="_blank" >https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1624299/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fimmu.2025.1624299" target="_blank" >10.3389/fimmu.2025.1624299</a>

Result language

angličtina

Original language name

Non-cognate ligands of hepatitis C virus envelope broadly neutralizing antibodies induce virus-neutralizing sera in mice

Original language description

Introduction The persistent rise in new Hepatitis C virus (HCV) infections threatens WHO efforts to eliminate HCV infection by 2030. Although direct-acting antiviral (DAA) drugs are efficacious, access remains limited, reinfections occur, and perinatal infections continue to pose long-term complications. Therefore, an effective anti-HCV vaccine is urgently needed.Methods We employed a highly complex combinatorial Myomedin-loop scaffold library to identify variants binding to paratopes of HCV E2-specific broadly neutralizing antibodies (bNAbs) HC-1AM and HC84.26.WH.5DL. The selected binders, named SHB and WIN, respectively, represent non-cognate mimotopes of the aforementioned bNAbs. These binders were subsequently used as immunogens in experimental mice to elicit serum antibodies capable of binding to HCV E2 and neutralize HCV pseudotyped viruses.Results and discussion The non-cognate mimotopes SHB and WIN competed with the E2 glycoprotein for bNAbs binding and, after immunizing experimental mice, elicited E2- and HCV-pseudovirus-specific antibodies. WIN- and SHB-immunized mice exhibited neutralization against 15 HCV pseudoviruses with varying neutralization sensitivities. The most potent binders WIN028 and WIN047, were modified with a C-terminal His-tag, allowing the generation of WIN proteoliposome and subsequent use in experimental mice immunizations. Hyperimmune sera exhibited improved binding to HCV E2 and neutralized 60% of the tested HCV pseudoviruses. The broad neutralization of HCV pseudoviruses achieved by hypperimmune sera from SHB- and WIN-immunized mice highlights the potential of this approach in the HCV vaccine design.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30102 - Immunology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Frontiers in Immunology

ISSN

1664-3224

e-ISSN

1664-3224

Volume of the periodical

16

Issue of the periodical within the volume

JUL 22 2025

Country of publishing house

CH - SWITZERLAND

Number of pages

14

Pages from-to

1624299

UT code for WoS article

001543589300001

EID of the result in the Scopus database

2-s2.0-105012599886