Head-to-head comparison of modular vaccines developed using different capsid virus-like particle backbones and antigen conjugation systems

Laurits Fredsgaard, Louise Goksøyr, Susan Thrane, Kara Lee Aves, Thor G. Theander, Adam F. Sander*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

6 Citations (Scopus)
62 Downloads (Pure)

Abstract

Capsid virus-like particles (cVLPs) are used as molecular scaffolds to increase the immunogenicity of displayed antigens. Modular platforms have been developed whereby antigens are attached to the surface of pre-assembled cVLPs. However, it remains unknown to what extent the employed cVLP backbone and conjugation system may influence the immune response elicited against the displayed antigen. Here, we performed a head-to-head comparison of antigen-specific IgG responses elicited by modular cVLP-vaccines differing by their employed cVLP backbone or conjugation system, respectively. Covalent antigen conjugation (i.e., employing the SpyTag/SpyCatcher system) resulted in significantly higher antigen-specific IgG titers compared to when using affinity-based conjugation (i.e., using biotin/streptavidin). The cVLP backbone also influenced the antigen-specific IgG response. Specifically, vaccines based on the bacteriophage AP205 cVLP elicited significantly higher antigen-specific IgG compared to corresponding vaccines using the human papillomavirus major capsid protein (HPV L1) cVLP. In addition, the AP205 cVLP platform mediated induction of antigen-specific IgG with a different subclass profile (i.e., higher IgG2a and IgG2b) compared to HPV L1 cVLP. These results demonstrate that the cVLP backbone and conjugation system can individually affect the IgG response elicited against a displayed antigen. These data will aid the understanding and process of tailoring modular cVLP vaccines to achieve improved immune responses.

Original languageEnglish
Article number539
JournalVaccines
Volume9
Issue number6
Number of pages11
ISSN2076-393X
DOIs
Publication statusPublished - Jun 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Conjugation system
  • Modular vaccine platform
  • Vaccine
  • Vaccine design
  • Virus-like particle

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