Malaria, a disease responsible for immense human suffering, is caused by infection with Plasmodium spp. parasites, which have a very complex life cycle - antigenically unique stages infect different tissues of the body. This review details recent developments in our understanding of immunity both to pre-erythrocytic stage antigens and to erythrocytic stage antigens. The former is largely mediated via CD8(+) T cells and involves IFN-gamma, nitric oxide, IL-12 and natural killer cells; the latter varies (in different hosts and with different parasites) but is largely mediated by antibody, helper T cells, nitric oxide and gammadelta T cells. The recent progress towards clinical trials of vaccine candidates against both the pre-erythrocytic stage and erythrocytic stage is also summarized, in particular the use of heterologous prime/boost strategies for the former and the use of MSP1 as a candidate vaccine for the latter.
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http://dx.doi.org/10.1016/S0952-7915(99)80069-7 | DOI Listing |
Lancet Infect Dis
December 2024
Department of Biochemistry and Kavli Institute for Nanoscience Discovery and the NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK. Electronic address:
Background: Two pre-erythrocytic vaccines (R21/Matrix-M and RTS,S/AS01) are now approved for Plasmodium falciparum malaria. However, neither induces blood-stage immunity against parasites that break through from the liver. RH5.
View Article and Find Full Text PDFNPJ Vaccines
December 2024
Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
Vaccines targeting the complex pre-erythrocytic stage of Plasmodium parasites may benefit from the inclusion of multiple antigens. However, discerning protective effects can be difficult because newer candidates may not be as protective as leading antigens like the circumsporozoite protein (CSP) in the conventional pre-clinical mouse model. We developed a modified mouse model challenge strategy that maximizes the contribution of T cells induced by novel candidate antigens at the sporozoite challenge time point and used this approach to test Plasmodium P36 and P52 vaccine candidates alone and in concert with non-protective doses of CSP.
View Article and Find Full Text PDFNat Commun
December 2024
Center for Global Health and Diseases, Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, USA.
New therapeutics are necessary for preventing Plasmodium vivax malaria due to easy transmissibility and dormancy in the liver that increases the clinical burden due to recurrent relapse. In this manuscript we characterize 12 Pv Apical Membrane Antigen 1 (PvAMA1) specific human monoclonal antibodies from Peripheral Blood Mononuclear Cells of a Pv-exposed individual. PvAMA1 is essential for sporozoite and merozoite invasion, making it a unique therapeutic target.
View Article and Find Full Text PDFJ Med Chem
November 2024
Gulbenkian Institute for Molecular Medicine, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal.
Preclinical and/or clinical studies have demonstrated the potential of Ivermectin (IVM) for malaria control. In order to improve its antiplasmodial activity and build on previous knowledge, we have designed a third generation of hybrid molecules in which selected pharmacophores were appended to the IVM macrolide, while retaining one or both sugar moieties at the C-13 position. Moreover, we synthesized IVM hybrids that contain structural features of potent IVM metabolites.
View Article and Find Full Text PDFRes Sq
September 2024
Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States of America.
Vaccines targeting the complex pre-erythrocytic stage of parasites may benefit from inclusion of multiple antigens. However, discerning protective effects can be difficult because newer candidates may not be as protective as leading antigens like the circumsporozoite protein (CSP) in the conventional pre-clinical mouse model. We developed a modified mouse model challenge strategy that maximizes the contribution of T cells induced by novel candidate antigens at the sporozoite challenge time point and used this approach to test P36 and P52 vaccine candidates alone and in concert with non-protective doses of CSP.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!