Immunization with apical membrane antigen 1 confers sterile infection-blocking immunity against Plasmodium sporozoite challenge in a rodent model

Schussek, Sophie, Trieu, Angela, Apte, Simon H., Sidney, John, Sette, Alessandro, and Doolan, Denise L. (2013) Immunization with apical membrane antigen 1 confers sterile infection-blocking immunity against Plasmodium sporozoite challenge in a rodent model. Infection and Immunity, 81 (10). pp. 3586-3599.

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Abstract

Apical membrane antigen 1 (AMA-1) is a leading blood-stage malaria vaccine candidate. Consistent with a key role in erythrocytic invasion, AMA-1-specific antibodies have been implicated in AMA-1-induced protective immunity. AMA-1 is also expressed in sporozoites and in mature liver schizonts where it may be a target of protective cell-mediated immunity. Here, we demonstrate for the first time that immunization with AMA-1 can induce sterile infection-blocking immunity against Plasmodium sporozoite challenge in 80% of immunized mice. Significantly higher levels of gamma interferon (IFN-γ)/interleukin-2 (IL-2)/tumor necrosis factor (TNF) multifunctional T cells were noted in immunized mice than in control mice. We also report the first identification of minimal CD8⁺ and CD4⁺ T cell epitopes on Plasmodium yoelii AMA-1. These data establish AMA-1 as a target of both preerythrocytic- and erythrocytic-stage protective immune responses and validate vaccine approaches designed to induce both cellular and humoral immunity.

Item ID: 41432
Item Type: Article (Refereed Research - C1)
ISSN: 1098-5522
Funders: University of Queensland (UQ) International Research Tuition Award, Australian Centre for Vaccine Development (ACVD), National Health and Medical Research Council (NHMRC), Pfizer Australia Senior Research Fellowship (PASRF), Queensland Tropical Health Alliance (QTHA)
Date Deposited: 24 Mar 2016 05:33
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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