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circumsporozoite protein

Structural basis of Plasmodium vivax inhibition by antibodies binding to the circumsporozoite protein repeats

January 18, 2022 - 21:14 -- Open Access
Kucharska I, Hossain L, Ivanochko D, Yang Q, Rubinstein JL, Pomès R, Julien JP
Elife. 2022 Jan 13;11:e72908

Malaria is a global health burden, with Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) responsible for the majority of infections worldwide. Circumsporozoite protein (CSP) is the most abundant protein on the surface of Plasmodium sporozoites, and antibodies targeting the central repeat region of CSP can prevent parasite infection. Although much has been uncovered about the molecular basis of antibody recognition of the PfCSP repeats, data remains scarce for PvCSP.

Serological responses to a soluble recombinant circumsporozoite protein-VK210 of Plasmodium vivax (rPvCSP-VK210) among Iranian malaria patients

December 1, 2021 - 20:30 -- Open Access
Nateghpour M, Etemadi S, Motevalli Haghi A, Eslami H, Mohebali M, Farivar L
Eur J Med Res. 2021 Nov 25;26(1):134

Circumsporozoite protein (CSP) has a central immune domain that includes short regions of repeating amino acid sequences. This immunodynamic region is an epitope of B cells that can elicit an immune response in human and laboratory animals. The aim of the present study was to express the recombinant PvCSP-VK210 antigen and evaluate it for assaying antibodies obtained during human P. vivax infection by Western blotting and indirect ELISA (enzyme-linked immunosorbent assay).

Subclass and avidity of circumsporozoite protein specific antibodies associate with protection status against malaria infection

September 1, 2021 - 17:10 -- Open Access
Seaton KE, Spreng RL, Abraha M, Reichartz M, Dennison SM, et al.
NPJ Vaccines. 2021 Aug 30;6(1):110

RTS,S/AS01 is an advanced pre-erythrocytic malaria vaccine candidate with demonstrated vaccine efficacy up to 86.7% in controlled human malaria infection (CHMI) studies; however, reproducible immune correlates of protection (CoP) are elusive. To identify candidates of humoral correlates of vaccine mediated protection, we measured antibody magnitude, subclass, and avidity for Plasmodium falciparum (Pf) circumsporozoite protein (CSP) by multiplex assays in two CHMI studies with varying RTS,S/AS01B vaccine dose and timing regimens.

Not Open Access | Plasmodium pre-erythrocytic vaccine antigens enhance sterile protection in mice induced by circumsporozoite protein

July 28, 2021 - 14:28 -- NOT Open Access
Daniel S, Pichugin A, Duffy PE, et al.
Infect Immun. 2021 Jul 26:IAI0016521

Pre-erythrocytic vaccines prevent malaria by targeting parasites in the clinically silent sporozoite and liver stages and preventing progression to the virulent blood stages. The leading pre-erythrocytic vaccine RTS,S/AS01E (Mosquirix®) entered implementation programs in 2019 and targets the major sporozoite surface antigen called circumsporozoite protein or CSP.

NOT Open Access | Epitope-Specific Antibody Responses to a Plasmodium falciparum Subunit Vaccine Target in a Malaria-Endemic Population

June 9, 2021 - 07:28 -- NOT Open Access
Friedman-Klabanoff DJ, Travassos MA, Berry AA, et al.
J Infect Dis. 2021 Jun 4;223(11):1943-1947

Circumsporozoite protein (CSP) coats the Plasmodium falciparum sporozoite surface and is a major malaria subunit vaccine target. We measured epitope-specific reactivity to field-derived CSP haplotypes in serum samples from Malian adults and children on a custom peptide microarray. Compared to children, adults showed greater antibody responses and responses to more variants in regions proximal to and within the central repeat region.

NOT open Access | Partial protection against P. vivax infection diminishes hypnozoite burden and blood-stage relapses

May 19, 2021 - 13:32 -- NOT Open Access
Schäfer C, Dambrauskas N, Sather DN, et al.
Cell Host Microbe. 2021 May 12;29(5):752-756.e4

Latent forms of Plasmodium vivax, called hypnozoites, cause malaria relapses from the liver into the bloodstream and are a major obstacle to malaria eradication. To experimentally assess the impact of a partially protective pre-erythrocytic vaccine on reducing Plasmodium vivax relapses, we developed a liver-humanized mouse model that allows monitoring of relapses directly in the blood. We passively infused these mice with a suboptimal dose of an antibody that targets the circumsporozoite protein prior to challenge with P. vivax sporozoites.

Malaria and Cancer: a critical review on the established associations and new perspectives

May 19, 2021 - 13:28 -- Open Access
Ellis T, Eze E, Raimi-Abraham BT
Infect Agent Cancer. 2021 May 13;16(1):33

Cancer and malaria both have high incidence rates and are leading causes of mortality worldwide, especially in low and middle-income countries with reduced access to the quality healthcare. The objective of this critical review was to summarize key associations and new perspectives between the two diseases as is reported in existing literature.

A VLP for validation of the Plasmodium falciparum circumsporozoite protein junctional epitope for vaccine development

April 6, 2021 - 14:24 -- Open Access
Atcheson E, Hill AVS, Reyes-Sandoval A
NPJ Vaccines. 2021 Apr 1;6(1):46

Malaria continues to be a pressing global health issue, causing nearly half a million deaths per year. An effective malaria vaccine could radically improve our ability to control and eliminate this pathogen. The most advanced malaria vaccine, RTS,S, confers only 30% protective efficacy under field conditions, and hence the search continues for improved vaccines.

Mechanisms and targets of Fcgamma-receptor mediated immunity to malaria sporozoites

March 23, 2021 - 14:49 -- Open Access
Feng G, Wines BD, Beeson JG, et al.
Nat Commun. 2021 Mar 19;12(1):1742

A highly protective vaccine will greatly facilitate achieving and sustaining malaria elimination. Understanding mechanisms of antibody-mediated immunity is crucial for developing vaccines with high efficacy. Here, we identify key roles in humoral immunity for Fcγ-receptor (FcγR) interactions and opsonic phagocytosis of sporozoites. We identify a major role for neutrophils in mediating phagocytic clearance of sporozoites in peripheral blood, whereas monocytes contribute a minor role.

Fluorescent tagging of Plasmodium circumsporozoite protein allows imaging of sporozoite formation but blocks egress from oocysts

February 23, 2021 - 13:06 -- Open Access
Singer M, Frischknecht F
Cell Microbiol. 2021 Feb 18:e13321

The circumsporozoite protein, CSP is the major surface protein of Plasmodium sporozoites, the form of malaria parasites transmitted by mosquitoes. CSP is involved in sporozoite formation within and egress from oocysts, entry into mosquito salivary glands and mammalian liver as well as migration in the skin. Yet, how CSP facilitates sporozoite formation, oocyst egress and hepatocyte specific invasion is still not fully understood.


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