title: Persistence and immunogenicity of chemically attenuated blood stage Plasmodium falciparum in Aotus monkeys.
abstract: Malaria is a disease caused by a protozoan of the Plasmodium genus and results in 0.5-0.7million deaths per year. Increasing drug resistance of the parasite and insecticide resistance of mosquitoes necessitate alternative control measures. Numerous vaccine candidates have been identified but none have been able to induce robust, long-lived protection when evaluated in malaria endemic regions. Rodent studies have demonstrated that chemically attenuated blood stage parasites can persist at sub-patent levels and induce homologous and heterologous protection against malaria. Parasite-specific cellular responses were detected, with protection dependent on CD4+ T cells. To investigate this vaccine approach for Plasmodium falciparum, we characterised the persistence and immunogenicity of chemically attenuated P. falciparum FVO strain parasites (CAPs) in non-splenectomised Aotus nancymaae monkeys following administration of a single dose. Control monkeys received either normal red blood cells or wild-type parasites followed by drug treatment. Chemical attenuation was performed using tafuramycin A, which irreversibly binds to DNA. CAPs were detected in the peripheral blood for up to 2days following inoculation as determined by thick blood smears, and for up to 8days as determined by quantitative PCR. Parasite-specific IgG was not detected in monkeys that received CAPs; however, in vitro parasite-specific T cell proliferation was observed. Following challenge, the CAP monkeys developed an infection; however, one CAP monkey and the infection and drug-cure monkeys showed partial or complete resistance. These experiments lay the groundwork for further assessment of CAPs as a potential vaccine against malaria.
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast Campus, Queensland, Australia.
authors.forename: Sai Lata
authors.initials: SL
authors.lastname: De
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast Campus, Queensland, Australia.
authors.forename: Danielle I
authors.initials: DI
authors.lastname: Stanisic
authors.affiliation: Department of Drug Evaluation, Australian Army Malaria Institute, Enoggera, Brisbane, Queensland, Australia.
authors.forename: Karin
authors.initials: K
authors.lastname: van Breda
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast Campus, Queensland, Australia.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Bellete
authors.affiliation: Department of Drug Evaluation, Australian Army Malaria Institute, Enoggera, Brisbane, Queensland, Australia.
authors.forename: Ivor
authors.initials: I
authors.lastname: Harris
authors.affiliation: Department of Drug Evaluation, Australian Army Malaria Institute, Enoggera, Brisbane, Queensland, Australia.
authors.forename: Fiona
authors.initials: F
authors.lastname: McCallum
authors.affiliation: Department of Drug Evaluation, Australian Army Malaria Institute, Enoggera, Brisbane, Queensland, Australia.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Edstein
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast Campus, Queensland, Australia. Electronic address: michael.good@griffith.edu.au.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Good
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016054:DNA, Protozoan / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D000882:Haplorhini; D007074:Immunoglobulin G / Q000276:immunology; D026121:Indole Alkaloids / Q000494:pharmacology; D017780:Malaria Vaccines / Q000276:immunology* / Q000494:pharmacology; D016778:Malaria, Falciparum / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D010865:Pilot Projects; D010963:Plasmodium falciparum / Q000187:drug effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016054:DNA, Protozoan; D007074:Immunoglobulin G; D026121:Indole Alkaloids; D017780:Malaria Vaccines; C000597292:tafuramycin A
keywords: Aotus monkeys; Chemically attenuated parasites; Malaria; Plasmodium falciparum FVO; Tafuramycin-A; Whole parasite blood stage vaccine