The Complement System Contributes to Functional Antibody-Mediated Responses Induced by Immunization with Plasmodium falciparum Malaria Sporozoites

Infection and Immunity, Год журнала: 2018, Номер 86(7)

Опубликована: Май 4, 2018

ABSTRACT Long-lasting and sterile homologous protection against malaria can be achieved by the exposure of malaria-naive volunteers under chemoprophylaxis to Plasmodium falciparum -infected mosquitoes (chemoprophylaxis sporozoite [CPS] immunization). While CPS-induced antibodies neutralize infectivity in vitro vivo , antibody-mediated effector mechanisms are still poorly understood. Here, we investigated whether complement contributes preerythrocytic immunity. Sera collected before after CPS immunization presence active or inactive were assessed for recognition NF54 heterologous NF135.C10 sporozoites, fixation, lysis, possible subsequent effects on human hepatocytes. induced sporozoite-specific IgM ( P < 0.0001) IgG = 0.001) with complement-fixing capacities 0.0001). Sporozoite lysis 0.017), traversal 0.0001), hepatocyte invasion inhibition strongly enhanced complement. Complement-mediated negatively correlated cumulative parasitemia during immunizations 0.013). similarly recognized binding sporozoites was reduced 0.023). Although did not differ their abilities fix complement, lyse inhibit more inhibited 0.008). These findings demonstrate that have activity, thereby significantly further enhancing functional . The combined data highlight importance as an additional immune mechanism immunity whole-parasite malaria.

Язык: Английский

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The transportome of the malaria parasite

Biological reviews/Biological reviews of the Cambridge Philosophical Society, Год журнала: 2019, Номер 95(2), С. 305 - 332

Опубликована: Ноя. 7, 2019

ABSTRACT Membrane transport proteins, also known as transporters, control the movement of ions, nutrients, metabolites, and waste products across membranes a cell are central to its biology. Proteins this type serve drug targets key players in phenomenon resistance. The malaria parasite has relatively reduced transportome, with only approximately 2.5% genes encoding transporters. Even so, assigning functions physiological roles these ascertaining their contributions action resistance, been very challenging. This review presents detailed critique synthesis disruption phenotypes, protein subcellular localisations, (observed or predicted), links antimalarial resistance for each parasite's transporter genes. breadth depth gene data particularly impressive, at least one phenotype determined asexual blood stage gene, multiple phenotypes available 76% Analysis curated set revealed there be little redundancy Plasmodium transportome; almost two‐thirds essential required normal growth parasite, proportion increased 78% when other life stages were included analysis. These observations, together finding that 22% transportome is implicated existing antimalarials and/or drugs within development pipeline, indicate transporters likely serve, already serving, targets. Integration different biological bioinformatic sets enabled selection candidates processes survival, but which underlying proteins have thus far remained undiscovered. include potential pantothenate, isoleucine, isopentenyl diphosphate, well putative anion‐selective channels may pore component ‘new permeation pathways’. Other novel insights into biology identification treatments, transmission‐blocking drugs, prophylactics, genetically attenuated vaccines. syntheses presented herein foundation elucidating members and, ultimately, explore realise therapeutic

Язык: Английский

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Plasmodium sporozoites on the move: Switching from cell traversal to productive invasion of hepatocytes

Molecular Microbiology, Год журнала: 2020, Номер 115(5), С. 870 - 881

Опубликована: Ноя. 16, 2020

Abstract Parasites of the genus Plasmodium , etiological agent malaria, are transmitted through bite anopheline mosquitoes, which deposit sporozoites into host skin. Sporozoites migrate dermis, enter bloodstream, and rapidly traffic to liver. They cross liver sinusoidal barrier traverse several hepatocytes before switching productive invasion a final one for replication inside parasitophorous vacuole. Cell traversal functionally independent processes that require proteins secreted from specialized secretory organelles known as micronemes. In this review, we summarize current understanding how cells productively invade hepatocytes, discuss role environmental sensing in migratory an invasive state. We propose timely controlled secretion distinct microneme subsets could play key successful migration infection hepatocytes. A better these essential biological features sporozoite may contribute development new strategies fight against very first asymptomatic stage malaria.

Язык: Английский

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What Is Known about the Immune Response Induced by Plasmodium vivax Malaria Vaccine Candidates?

Frontiers in Immunology, Год журнала: 2017, Номер 8

Опубликована: Фев. 13, 2017

Malaria caused by Plasmodium vivax continues being one of the most important infectious diseases around world; P. is second prevalent species and has greatest geographic distribution. Developing an effective antimalarial vaccine considered a relevant control strategy in search for means preventing disease. Studying parasite expressed proteins which are essential host cell invasion led to identifying regions recognised individuals who naturally exposed infection. Furthermore, immunogenicity studies have revealed that such can trigger robust immune response inhibit sporozoite (haepatic stage) or merozoite (erythrocyte induce protection. This review provides synthesis date concerning antigenicity both synthetic peptide recombinant protein candidates against malaria produced vivax.

Язык: Английский

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Humoral protection against mosquito bite-transmitted Plasmodium falciparum infection in humanized mice

npj Vaccines, Год журнала: 2017, Номер 2(1)

Опубликована: Окт. 4, 2017

A malaria vaccine that prevents infection will be an important new tool in continued efforts of elimination, and such vaccines are under intense development for the major human parasite Plasmodium falciparum (Pf). Antibodies elicited by can block initial phases when sporozoites deposited into skin mosquito bite then target liver further development. However, there currently no standardized vivo preclinical models measure inhibitory activity antibody specificities against Pf sporozoite via bite. Here, we use liver-chimeric mice as a challenge model to assess prevention natural antibodies. We demonstrate these consistently infected with this combined passive transfer either monoclonal antibodies or polyclonal IgG from immune serum antibody-mediated blocking using bioluminescent imaging. This methodology is useful down-select functional investigate mechanisms correlates protection clinical trials, thereby informing rational optimization.

Язык: Английский

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