AUTHOR=Pattinson David J. , Apte Simon H. , Wibowo Nani , Chuan Yap P. , Rivera-Hernandez Tania , Groves Penny L. , Lua Linda H. , Middelberg Anton P. J. , Doolan Denise L. TITLE=Chimeric Murine Polyomavirus Virus-Like Particles Induce Plasmodium Antigen-Specific CD8+ T Cell and Antibody Responses JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=9 YEAR=2019 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2019.00215 DOI=10.3389/fcimb.2019.00215 ISSN=2235-2988 ABSTRACT=

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.