Recombinant Flag-tagged E1E2 glycoproteins from three hepatitis C virus genotypes are biologically functional and elicit cross-reactive neutralizing antibodies in mice

Hepatitis C virus (HCV) is a globally disseminated human pathogen for which no vaccine is currently available. HCV is highly diverse genetically and can be classified into 7 genotypes and multiple sub-types. Due to this antigenic variation, the induction of cross-reactive and at the same time neutra...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2018-06, Vol.519, p.33-41
Main Authors: Krapchev, Vasil B., Rychłowska, Malgorzata, Chmielewska, Alicja, Zimmer, Karolina, Patel, Arvind H., Bieńkowska-Szewczyk, Krystyna
Format: Article
Language:English
Subjects:
Animals
Antibodies, Neutralizing - biosynthesis
Antibodies, Neutralizing - immunology
Antibodies, Viral - immunology
Cell Line
Cross Reactions
E1E2
Envelope glycoproteins
Epitope Mapping
Epitopes - immunology
Flag tag
Genotype
Hepacivirus - genetics
Hepacivirus - immunology
Hepacivirus - physiology
Hepatitis C virus
Humans
Immunogenicity, Vaccine
Mice
Neutralization
Neutralization Tests
Receptors, Virus - metabolism
Recombinant Proteins - chemistry
Recombinant Proteins - immunology
Tetraspanin 28 - metabolism
Vaccine
Viral Envelope Proteins - chemistry
Viral Envelope Proteins - genetics
Viral Envelope Proteins - immunology
Viral Envelope Proteins - metabolism
Virus Internalization
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Summary:Hepatitis C virus (HCV) is a globally disseminated human pathogen for which no vaccine is currently available. HCV is highly diverse genetically and can be classified into 7 genotypes and multiple sub-types. Due to this antigenic variation, the induction of cross-reactive and at the same time neutralizing antibodies is a challenge in vaccine production. Here we report the analysis of immunogenicity of recombinant HCV envelope glycoproteins from genotypes 1a, 1b and 2a, with a Flag tag inserted in the hypervariable region 1 of E2. This modification did not affect protein expression or conformation or its capacity to bind the crucial virus entry factor, CD81. Importantly, in immunogenicity studies on mice, the purified E2-Flag mutants elicited high-titer, cross-reactive antibodies that were able to neutralize HCV infectious particles from two genotypes tested (1a and 2a). These findings indicate that E1E2-Flag envelope glycoproteins could be important immunogen candidates for vaccine aiming to induce broad HCV-neutralizing responses.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2018.03.026