title: Comparative assessment of vaccine vectors encoding ten malaria antigens identifies two protective liver-stage candidates.
abstract: The development of an efficacious Plasmodium falciparum malaria vaccine remains a top priority for global health. Vaccination with irradiated sporozoites is able to provide complete sterile protection through the action of CD8(+) T cells at the liver-stage of infection. However, this method is currently unsuitable for large-scale deployment and focus has instead turned to the development of sub-unit vaccines. Sub-unit vaccine efforts have traditionally focused on two well-known pre-erythrocytic antigens, CSP and TRAP, yet thousands of genes are expressed in the liver-stage. We sought to assess the ability of eight alternative P. falciparum pre-erythrocytic antigens to induce a high proportion of CD8(+) T cells. We show that all antigens, when expressed individually in the non-replicating viral vectors ChAd63 and MVA, are capable of inducing an immune response in mice. Furthermore, we also developed chimeric P. berghei parasites expressing the cognate P. falciparum antigen to enable assessment of efficacy in mice. Our preliminary results indicate that vectors encoding either PfLSA1 or PfLSAP2 are capable of inducing sterile protection dependent on the presence of CD8(+) T cells. This work has identified two promising P. falciparum liver-stage candidate antigens that will now undergo further testing in humans.
authors.affiliation: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, United Kingdom.
authors.forename: Rhea J
authors.initials: RJ
authors.lastname: Longley
authors.affiliation: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, United Kingdom.|Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Salman
authors.affiliation: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, United Kingdom.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Cottingham
authors.affiliation: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, United Kingdom.
authors.forename: Katie
authors.initials: K
authors.lastname: Ewer
authors.affiliation: Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Janse
authors.affiliation: Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
authors.forename: Shahid M
authors.initials: SM
authors.lastname: Khan
authors.affiliation: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, United Kingdom.
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Spencer
authors.affiliation: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, United Kingdom.
authors.forename: Adrian V S
authors.initials: AVS
authors.lastname: Hill
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005822:Genetic Vectors; D000949:Histocompatibility Antigens Class II / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D008099:Liver / Q000276:immunology; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D051379:Mice; D010963:Plasmodium falciparum / Q000276:immunology / Q000472:pathogenicity; D014611:Vaccination
chemical_list: D000953:Antigens, Protozoan; D000949:Histocompatibility Antigens Class II; D017780:Malaria Vaccines; C067302:liver stage-specific antigen, Plasmodium