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- Title
Induction of cross-neutralizing antibodies by a permuted hepatitis C virus glycoprotein nanoparticle vaccine candidate.
- Authors
Sliepen, Kwinten; Radić, Laura; Capella-Pujol, Joan; Watanabe, Yasunori; Zon, Ian; Chumbe, Ana; Lee, Wen-Hsin; de Gast, Marlon; Koopsen, Jelle; Koekkoek, Sylvie; del Moral-Sánchez, Iván; Brouwer, Philip J. M.; Ravichandran, Rashmi; Ozorowski, Gabriel; King, Neil P.; Ward, Andrew B.; van Gils, Marit J.; Crispin, Max; Schinkel, Janke; Sanders, Rogier W.
- 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. E1E2 spike on the hepatitis C virion is an important target for vaccine design. Here, the authors permute the subunits to generate E2E1 immunogens and show that mosaic nanoparticles displaying different E2E1 antigens elicit cross-neutralizing antibodies in rabbits.
- Subjects
HEPATITIS C virus; NANOPARTICLES; IMMUNOGLOBULINS; ANTIBODY formation; HEPATITIS C; MONOCLONAL antibodies
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-34961-8