Frontiers in Cellular and Infection Microbiology (Jun 2019)

Chimeric Murine Polyomavirus Virus-Like Particles Induce Plasmodium Antigen-Specific CD8+ T Cell and Antibody Responses

  • David J. Pattinson,
  • David J. Pattinson,
  • Simon H. Apte,
  • Nani Wibowo,
  • Yap P. Chuan,
  • Tania Rivera-Hernandez,
  • Penny L. Groves,
  • Linda H. Lua,
  • Anton P. J. Middelberg,
  • Denise L. Doolan,
  • Denise L. Doolan

DOI
https://doi.org/10.3389/fcimb.2019.00215
Journal volume & issue
Vol. 9

Abstract

Read online

An effective vaccine against the Plasmodium parasite is likely to require the induction of robust antibody and T cell responses. Chimeric virus-like particles are an effective vaccine platform for induction of antibody responses, but their capacity to induce robust cellular responses and cell-mediated protection against pathogen challenge has not been established. To evaluate this, we produced chimeric constructs using the murine polyomavirus structural protein with surface-exposed CD8+ or CD4+ T cell or B cell repeat epitopes derived from the Plasmodium yoelii circumsporozoite protein, and assessed immunogenicity and protective capacity in a murine model. Robust CD8+ T cell responses were induced by immunization with the chimeric CD8+ T cell epitope virus-like particles, however CD4+ T cell responses were very low. The B cell chimeric construct induced robust antibody responses but there was no apparent synergy when T cell and B cell constructs were administered as a pool. A heterologous prime/boost regimen using plasmid DNA priming followed by a VLP boost was more effective than homologous VLP immunization for cellular immunity and protection. These data show that chimeric murine polyomavirus virus-like particles are a good platform for induction of CD8+ T cell responses as well as antibody responses.

Keywords