Induction of cross-neutralizing antibodies by a permuted hepatitis C virus glycoprotein nanoparticle vaccine candidate

Kwinten Sliepen, Laura Radić, Joan Capella-Pujol, Yasunori Watanabe, Ian Zon, Ana Chumbe, Wen-Hsin Lee, Marlon de Gast, Jelle Koopsen, Sylvie Koekkoek, Iván del Moral-Sánchez, Philip J. M. Brouwer, Rashmi Ravichandran, Gabriel Ozorowski, Neil P. King, Andrew B. Ward, Marit J. van Gils, Max Crispin, Janke Schinkel, Rogier W. Sanders

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Scopus)

Abstract

Hepatitis C virus (HCV) infection affects approximately 58 million people and causes ~300,000 deaths yearly. The only target for HCV neutralizing antibodies is the highly sequence diverse E1E2 glycoprotein. Eliciting broadly neutralizing antibodies that recognize conserved cross-neutralizing epitopes is important for an effective HCV vaccine. However, most recombinant HCV glycoprotein vaccines, which usually include only E2, induce only weak neutralizing antibody responses. Here, we describe recombinant soluble E1E2 immunogens that were generated by permutation of the E1 and E2 subunits. We displayed the E2E1 immunogens on two-component nanoparticles and these nanoparticles induce significantly more potent neutralizing antibody responses than E2. Next, we generated mosaic nanoparticles co-displaying six different E2E1 immunogens. These mosaic E2E1 nanoparticles elicit significantly improved neutralization compared to monovalent E2E1 nanoparticles. These results provide a roadmap for the generation of an HCV vaccine that induces potent and broad neutralization.
Original languageEnglish
Article number7271
JournalNature communications
Volume13
Issue number1
DOIs
Publication statusPublished - 1 Dec 2022

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