A master lock for deadly parasites

Tham, Wai‐Hong; Kennedy, Alexander T.

doi:10.1038/522158a

Cited by 9 publications

(5 citation statements)

References 10 publications

(4 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In P. falciparum, there are redundant functions in the individual members of these protein families that need to be considered in the process of selecting vaccine candidates [25]. For example, the 175-kDa EBA (EBA175) binds to glycophorin A on the erythrocyte surface, whereas Rh4 binds to CR1 [26]. After parasite reorientation, Rh5 forms a complex with Rh5-interacting protein (Ripr) [27] and cysteine-rich protective antigen (CyRPA) [28].…”

Section: Figurementioning

confidence: 99%

The Need for Novel Asexual Blood-Stage Malaria Vaccine Candidates for Plasmodium falciparum

Takashima,

Otsuki,

Morita

et al. 2024

Biomolecules

View full text Add to dashboard Cite

Extensive control efforts have significantly reduced malaria cases and deaths over the past two decades, but in recent years, coupled with the COVID-19 pandemic, success has stalled. The WHO has urged the implementation of a number of interventions, including vaccines. The modestly effective RTS,S/AS01 pre-erythrocytic vaccine has been recommended by the WHO for use in sub-Saharan Africa against Plasmodium falciparum in children residing in moderate to high malaria transmission regions. A second pre-erythrocytic vaccine, R21/Matrix-M, was also recommended by the WHO on 3 October 2023. However, the paucity and limitations of pre-erythrocytic vaccines highlight the need for asexual blood-stage malaria vaccines that prevent disease caused by blood-stage parasites. Few asexual blood-stage vaccine candidates have reached phase 2 clinical development, and the challenges in terms of their efficacy include antigen polymorphisms and low immunogenicity in humans. This review summarizes the history and progress of asexual blood-stage malaria vaccine development, highlighting the need for novel candidate vaccine antigens/molecules.

show abstract

Section: Figurementioning

confidence: 99%

The Need for Novel Asexual Blood-Stage Malaria Vaccine Candidates for Plasmodium falciparum

Takashima,

Otsuki,

Morita

et al. 2024

Biomolecules

View full text Add to dashboard Cite

show abstract

“…CD55 inhibition increases susceptibility to severe anemia, which possibly occurs due to the destruction of erythrocytes by the complement activation ( 77 ). Therefore, soluble forms of CD55 as a competitor to CD55 on the surface of erythrocytes have become an attractive target for the development of malaria therapeutics ( 78 ).…”

Section: Diseases Associated With Cd55mentioning

confidence: 99%

Beyond the Role of CD55 as a Complement Component

2018

View full text Add to dashboard Cite

The complement is a part of the immune system that plays several roles in removing pathogens. Despite the importance of the complement system, the exact role of each component has been overlooked because the complement system was thought to be a nonspecific humoral immune mechanism that worked against pathogens. Decay-accelerating factor (DAF or CD55) is a known inhibitor of the complement system and has recently attracted substantial attention due to its role in various diseases, such as cancer, protein-losing enteropathy, and malaria. Some protein-losing enteropathy cases are caused by CD55 deficiency, which leads to complement hyperactivation, malabsorption, and angiopathic thrombosis. In addition, CD55 has been reported to be an essential host receptor for infection by the malaria parasite. Moreover, CD55 is a ligand of the seven-span transmembrane receptor CD97. Since CD55 is present in various cells, the functional role of CD55 has been expanded by showing that CD55 is associated with a variety of diseases, including cancer, malaria, protein-losing enteropathy, paroxysmal nocturnal hemoglobinuria, and autoimmune diseases. This review summarizes the current understanding of CD55 and the role of CD55 in these diseases. It also provides insight into the development of novel drugs for the diagnosis and treatment of diseases associated with CD55.

show abstract

“…Two erythrocyte receptors, basigin (BSG) and CD55 are essential for parasite invasion of erythrocytes[86, 87], making them attractive therapeutic targets. However, any blockade of these receptors would have to account for their expression on other cell types, and their role in physiological processes in the body [88–90]. An alternative strategy that has been proposed is the use of soluble receptor [88], although recombinant proteins are expensive and present more complex storage issues than small molecule drugs for resource-poor settings.…”

Section: Host-targeted Therapy Against Parasite Invasion Of Erythrocytesmentioning

confidence: 99%

Opportunities for Host-targeted Therapies for Malaria

Glennon

Dankwa

Smith

et al. 2018

Trends in Parasitology

View full text Add to dashboard Cite

Despite the recent successes of artemisinin-based antimalarial drugs, many still die from severe malaria, and eradication efforts are hindered by the limited drugs currently available to target transmissible gametocyte parasites and liver-resident dormant Plasmodium vivax hypnozoites. Host-targeted therapy is a new direction for infectious disease drug development and aims to interfere with host molecules, pathways, or networks that are required for infection or that contribute to disease. Recent advances in our understanding of host pathways involved in parasite development and pathogenic mechanisms in severe malaria could facilitate the development of host-targeted interventions against Plasmodium infection and malaria disease. This review discusses new opportunities for host-targeted therapeutics for malaria and the potential to harness drug polypharmacology to simultaneously target multiple host pathways using a single drug intervention.

show abstract

A master lock for deadly parasites

Abstract: An RNA-interference screen has identified the protein CD55, expressed on the surface of red blood cells, as an essential receptor for infection of the cells by the malaria parasite Plasmodium falciparum.

Cited by 9 publications

References 10 publications

The Need for Novel Asexual Blood-Stage Malaria Vaccine Candidates for Plasmodium falciparum

The Need for Novel Asexual Blood-Stage Malaria Vaccine Candidates for Plasmodium falciparum

Beyond the Role of CD55 as a Complement Component

Opportunities for Host-targeted Therapies for Malaria

Contact Info

Product

Resources

About