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

Vasil B. Krapchev , Małgorzata Rychłowska , Alicja Chmielewska , Karolina Zimmer , Arvind H. Patel , Krystyna Bieńkowska-Szewczyk

Abstract

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.
Author Vasil B. Krapchev (IFB)
Vasil B. Krapchev,,
- Intercollegiate Faculty of Biotechnology UG
, Małgorzata Rychłowska (IFB / IB / LVMB)
Małgorzata Rychłowska,,
- Laboratory of Virus Molecular Biology
, Alicja Chmielewska (IFB / IB / LVMB)
Alicja Chmielewska,,
- Laboratory of Virus Molecular Biology
, Karolina Zimmer (IFB)
Karolina Zimmer,,
- Intercollegiate Faculty of Biotechnology UG
, Arvind H. Patel
Arvind H. Patel,,
-
, Krystyna Bieńkowska-Szewczyk (IFB / IB / LVMB)
Krystyna Bieńkowska-Szewczyk,,
- Laboratory of Virus Molecular Biology
Journal seriesVirology, ISSN 0042-6822, (A 25 pkt)
Issue year2018
Vol519
Pages33-41
Publication size in sheets0.5
Keywords in Englishhepatitis C virus, E1E2, envelope glycoproteins, Flag tag, neutralization, vaccine
DOIDOI:10.1016/j.virol.2018.03.026
URL https://doi.org/10.1016/j.virol.2018.03.026
Languageen angielski
LicenseOther; published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)30
ScoreMinisterial score = 25.0, 04-10-2018, ArticleFromJournal
Ministerial score (2013-2016) = 30.0, 04-10-2018, ArticleFromJournal
Publication indicators WoS Impact Factor: 2016 = 3.353 (2) - 2016=3.164 (5)
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