title: Assessment of the Plasmodium falciparum Preerythrocytic Antigen UIS3 as a Potential Candidate for a Malaria Vaccine.
abstract: Efforts are under way to improve the efficacy of subunit malaria vaccines through assessments of new adjuvants, vaccination platforms, and antigens. In this study, we further assessed thePlasmodium falciparumantigen upregulated in infective sporozoites 3 (PfUIS3) as a vaccine candidate. PfUIS3 was expressed in the viral vectors chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) and used to immunize mice in a prime-boost regimen. We previously demonstrated that this regimen could provide partial protection against challenge with chimericP. bergheiparasites expressing PfUIS3. We now show that ChAd63-MVA PfUIS3 can also provide partial cross-species protection against challenge with wild-typeP. bergheiparasites. We also show that PfUIS3-specific cellular memory responses could be recalled in human volunteers exposed toP. falciparumparasites in a controlled human malaria infection study. When ChAd63-MVA PfUIS3 was coadministered with the vaccine candidateP. falciparumthrombospondin-related adhesion protein (PfTRAP) expressed in the ChAd63-MVA system, there was no significant change in immunogenicity to either vaccine. However, when mice were challenged with double chimericP. berghei-P. falciparumparasites expressing both PfUIS3 and PfTRAP, vaccine efficacy was improved to 100% sterile protection. This synergistic effect was evident only when the two vaccines were mixed and administered at the same site. We have therefore demonstrated that vaccination with PfUIS3 can induce a consistent delay in patent parasitemia across mouse strains and against chimeric parasites expressing PfUIS3 as well as wild-typeP. berghei; when this vaccine is combined with another partially protective regimen (ChAd63-MVA PfTRAP), complete protection is induced.
authors.affiliation: The Jenner Institute, University of Oxford, Oxford, United Kingdom Longley.r@wehi.edu.au.
authors.forename: Rhea J
authors.identifier: http://orcid.org/0000-0002-4510-5602
authors.initials: RJ
authors.lastname: Longley
authors.affiliation: The Jenner Institute, University of Oxford, Oxford, United Kingdom.
authors.forename: Benedict R
authors.initials: BR
authors.lastname: Halbroth
authors.affiliation: The Jenner Institute, University of Oxford, Oxford, United Kingdom.|Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Salman
authors.affiliation: The Jenner Institute, University of Oxford, Oxford, United Kingdom.
authors.forename: Katie J
authors.initials: KJ
authors.lastname: Ewer
authors.affiliation: The Jenner Institute, University of Oxford, Oxford, United Kingdom.
authors.forename: Susanne H
authors.initials: SH
authors.lastname: Hodgson
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Janse
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Shahid M
authors.initials: SM
authors.lastname: Khan
authors.affiliation: The Jenner Institute, University of Oxford, Oxford, United Kingdom.
authors.forename: Adrian V S
authors.initials: AVS
authors.lastname: Hill
authors.affiliation: The Jenner Institute, University of Oxford, Oxford, United Kingdom.
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Spencer
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007114:Immunization; D007156:Immunologic Memory; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; C531995:UIS3 protein, Plasmodium falciparum; D019444:Vaccines, DNA
keywords: Plasmodium; UIS3; liver stage; malaria; sterile protection; synergy; vaccines