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 Gast, Jelle Koopsen, Sylvie Koekkoek, Iván Moral-Sánchez, Philip J. M. Brouwer, Rashmi Ravichandran, Gabriel Ozorowski, Neil P. King, Andrew B. Ward, Marit J. Gils, Max Crispin, Janke Schinkel and Rogier W. Sanders ()
Additional contact information
Kwinten Sliepen: Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
Laura Radić: Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
Joan Capella-Pujol: Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
Yasunori Watanabe: University of Southampton
Ian Zon: Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
Ana Chumbe: Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
Wen-Hsin Lee: The Scripps Research Institute
Marlon Gast: Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
Jelle Koopsen: Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
Sylvie Koekkoek: Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
Iván Moral-Sánchez: Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
Philip J. M. Brouwer: Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
Rashmi Ravichandran: University of Washington
Gabriel Ozorowski: The Scripps Research Institute
Neil P. King: University of Washington
Andrew B. Ward: The Scripps Research Institute
Marit J. Gils: Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
Max Crispin: University of Southampton
Janke Schinkel: Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
Rogier W. Sanders: Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-34961-8

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