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dc.contributor.authorWilson, Kirsty L
dc.contributor.authorPouniotis, Dodie
dc.contributor.authorHanley, Jennifer
dc.contributor.authorXiang, Sue D
dc.contributor.authorMa, Charles
dc.contributor.authorCoppel, Ross L
dc.contributor.authorPlebanski, Magdalena
dc.date.accessioned2019-07-12T04:35:59Z
dc.date.available2019-07-12T04:35:59Z
dc.date.issued2019
dc.identifier.issn1664-3224
dc.identifier.doi10.3389/fimmu.2019.00331
dc.identifier.urihttp://hdl.handle.net/10072/386360
dc.description.abstractMalaria remains a significant health problem in many tropical and sub-tropical regions. The development of vaccines against the clinically active blood-stage of infection needs to consider variability and polymorphism in target antigens, and an adjuvant system able to induce broad spectrum immunity comprising both antibodies and helper T cells. Moreover, recent studies have shown some conventional pro-inflammatory adjuvants can also promote expansion of immunosuppressive regulatory T cells (Treg) and myeloid derived suppressor cells (MDSC), both of which could negatively impact malaria disease progression. Herein, we explore the ability of a model nanoparticle delivery system (polystyrene nanoparticles; PSNPs), previously proven to not induce conventional inflammation, Treg or MDSC, to induce immunity to MSP4/5 from Plasmodium yoelii, a member of the MSP4 and MSP5 family of proteins which are highly conserved across diverse malaria species including P. falciparum. The results show PSNPs-MSP4/5 conjugates are highly immunogenic, inducing immune responses comprising both T helper 1 (Th1) and Th2 cellular immunity, and a spectrum of antibody subclasses including IgG1, IgG2a, and IgG2b. Benchmarked against Alum and Complete Freund's Adjuvant (CFA), the immune responses that were induced were of comparable or higher magnitude, for both T cell frequencies by ELISpot and antibody responses in terms of ELISA end titer. Importantly, immunization with PSNPs-MSP4/5 induced partial protection against malaria blood-stage infection (50–80%) shown to be mechanistically dependent on interferon gamma (IFN-γ) production. These results expand the scope of adjuvants considered for malaria blood-stage vaccine development to those that do not use conventional adjuvant pathways and emphasizes the critical role of cellular immunity and specifically IFN-γ producing cells in providing moderate protection against blood-stage malaria comparable to Freunds adjuvant.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherFRONTIERS MEDIA SA
dc.relation.ispartofpagefrom1
dc.relation.ispartofpageto12
dc.relation.ispartofissueArticle 331
dc.relation.ispartofjournalFRONTIERS IN IMMUNOLOGY
dc.relation.ispartofvolume10
dc.subject.fieldofresearchImmunology
dc.subject.fieldofresearchMedical Microbiology
dc.subject.fieldofresearchcode1107
dc.subject.fieldofresearchcode1108
dc.titleA Synthetic Nanoparticle Based Vaccine Approach Targeting MSP4/5 Is Immunogenic and Induces Moderate Protection Against Murine Blood-Stage Malaria
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.rights.copyright© 2019 Wilson, Pouniotis, Hanley, Xiang, Ma, Coppel and Plebanski. 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.
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gro.griffith.authorCoppel, Ross L.


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