Chimeric murine polyomavirus virus-like particles induce Plasmodium antigen-specific CD8+ T cell and antibody responses

Pattinson, David J., Apte, Simon H., Wibowo, Nani, Chuan, Yap P., Rivera-Hernandez, Tania, Groves, Penny L., Lua, Linda H., Middelberg, Anton P.J., and Doolan, Denise L. (2019) Chimeric murine polyomavirus virus-like particles induce Plasmodium antigen-specific CD8+ T cell and antibody responses. Frontiers in Cellular and Infection Microbiology, 9. 215.

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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.

Item ID: 60506
Item Type: Article (Research - C1)
ISSN: 2235-2988
Keywords: malaria, vaccine, circumsporozoite protein, virus-like particle, murine polyomavirus, cellular immunity, T cell responses, Plasmodium yoelii
Copyright Information: Copyright © 2019 Pattinson, Apte, Wibowo, Chuan, Rivera-Hernandez, Groves, Lua, Middelberg and Doolan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Funders: National Health and Medical Research Council of Australia (NHMRC), UQ-QIMR
Projects and Grants: NHMRC grant #1037304, NHMRC Principal Research Fellowship #1023636, UQ-QIMR Australian Infectious Diseases Grant
Date Deposited: 10 Oct 2019 01:02
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110704 Cellular Immunology @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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