Two-component vaccine consisting of virus-like particles displaying hepatitis C virus envelope protein 2 oligomers
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Development of B-cell-based hepatitis C virus (HCV) vaccines that induce broadly neutralizing antibodies (bNAbs) is hindered by extensive sequence diversity and low immunogenicity of envelope glycoprotein vaccine candidates, most notably soluble E2 (sE2). To overcome this, we employed two-component approaches using self-assembling virus-like particles (cVLPs; component 1), displaying monomeric or oligomeric forms of HCV sE2 (sE2mono or sE2oligo; component 2). Immunization studies were performed in BALB/c mice and the neutralizing capacity of vaccine-induced antibodies was tested in cultured-virus-neutralizations, using HCV of genotypes 1–6. sE2-cVLP vaccines induced significantly higher levels of NAbs (p = 0.0065) compared to corresponding sE2 vaccines. Additionally, sE2oligo-cVLP was superior to sE2mono-cVLP in inducing bNAbs. Interestingly, human monoclonal antibody AR2A had reduced binding in ELISA to sE2oligo-cVLP compared with sE2mono-cVLP and competition ELISA using mouse sera from vaccinated animals indicated that sE2oligo-cVLP induced significantly less non-bNAbs AR2A (p = 0.0043) and AR1B (p = 0.017). Thus, cVLP-displayed oligomeric sE2 shows promise as an HCV vaccine candidate.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 148 |
| Tidsskrift | npj Vaccines |
| Vol/bind | 7 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
The authors would like to thank Lotte Mikkelsen and Anne-Louise Sørensen (Copenhagen University Hospital, Hvidovre) and Anne Corfitz and Nahla Chehabi (Center for Medical Parasitology, UCPH) for technical assistance, Bjarne Ørskov Lindhardt (Copenhagen University Hospital, Hvidovre), and Carsten Geisler and Charlotte Menné Bonefeld (University of Copenhagen) for their support of the project and Mansun Law (Scripps Research Institute, US) and Charles Rice (Rockefeller University, US) for providing reagents. Furthermore, we would like to thank the Core Facility for Integrated Microscopy, Faculty of Health and Medical Sciences, University of Copenhagen for their support with the Transmission Electron Microscopy images, as well as the Biophysics Facility—Protein Structure and Function Program from Center for Protein Research, Copenhagen, for aiding with DLS measurements. This study was supported by funding from the Danish Cancer Society (R204-A12639 Project Grant to J.B.), the Lundbeck Foundation (R303-2018-3396 Postdoc Grant to R.V.M. and R335-2019-2052 Fellowship grant to J.P.), the Independent Research Fund Denmark (4004-00598 Advanced Grant to J.B. and 6110-00177B Project Grant to T.T., M.A.N., and A.F.S.), the Novo Nordisk Foundation NNF17OC0029372 Project Grant and NNF19OC0054518 Distinguished Investigator Grant both to J.B.) and by Eurostars, funded by the European commission and Innovation fund Denmark (E11019 to T.T., M.A.N., and A.F.S.).
Funding Information:
The authors would like to thank Lotte Mikkelsen and Anne-Louise Sørensen (Copenhagen University Hospital, Hvidovre) and Anne Corfitz and Nahla Chehabi (Center for Medical Parasitology, UCPH) for technical assistance, Bjarne Ørskov Lindhardt (Copenhagen University Hospital, Hvidovre), and Carsten Geisler and Charlotte Menné Bonefeld (University of Copenhagen) for their support of the project and Mansun Law (Scripps Research Institute, US) and Charles Rice (Rockefeller University, US) for providing reagents. Furthermore, we would like to thank the Core Facility for Integrated Microscopy, Faculty of Health and Medical Sciences, University of Copenhagen for their support with the Transmission Electron Microscopy images, as well as the Biophysics Facility—Protein Structure and Function Program from Center for Protein Research, Copenhagen, for aiding with DLS measurements. This study was supported by funding from the Danish Cancer Society (R204-A12639 Project Grant to J.B.), the Lundbeck Foundation (R303-2018-3396 Postdoc Grant to R.V.M. and R335-2019-2052 Fellowship grant to J.P.), the Independent Research Fund Denmark (4004-00598 Advanced Grant to J.B. and 6110-00177B Project Grant to T.T., M.A.N., and A.F.S.), the Novo Nordisk Foundation NNF17OC0029372 Project Grant and NNF19OC0054518 Distinguished Investigator Grant both to J.B.) and by Eurostars, funded by the European commission and Innovation fund Denmark (E11019 to T.T., M.A.N., and A.F.S.).
Publisher Copyright:
© 2022, The Author(s).
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