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B cell intrinsic expression of IFNlambda receptor suppresses the acute humoral immune response to experimental blood-stage malaria

December 2, 2020 - 09:49 -- Open Access
Hahn WO, Pepper M, Liles WC
Virulence. 2020 Dec;11(1):594-606

Antibodies play a critical protective role in the host response to blood-stage malaria infection. The role of cytokines in shaping the antibody response to blood-stage malaria is unclear. Interferon lambda (IFNλ), a type III interferon, is a cytokine produced early during blood-stage malaria infection that has an unknown physiological role during malaria infection.

Balancing in a black box: Potential immunomodulatory roles for TGF-beta signaling during blood-stage malaria

December 2, 2020 - 08:04 -- Open Access
Drewry LL, Harty JT
Virulence. 2020 Dec;11(1):159-169

Malarial disease caused by Plasmodium parasites challenges the mammalian immune system with a delicate balancing act. Robust inflammatory responses are required to control parasite replication within red blood cells, which if unchecked, can lead to severe anemia and fatality. However, the same inflammatory response that controls parasite replication is also associated with immunopathology and severe disease, as is exemplified by cerebral malaria.

Not Open Access | Designed Parasite-Selective Rhomboid Inhibitors Block Invasion and Clear Blood-Stage Malaria

November 24, 2020 - 13:37 -- NOT Open Access
Gandhi S, Baker RP, Cho S, Stanchev S, Strisovsky K, Urban S
Cell Chem Biol. 2020 Nov 19;27(11):1410-1424.e6

Rhomboid intramembrane proteases regulate pathophysiological processes, but their targeting in a disease context has never been achieved. We decoded the atypical substrate specificity of malaria rhomboid PfROM4, but found, unexpectedly, that it results from "steric exclusion": PfROM4 and canonical rhomboid proteases cannot cleave each other's substrates due to reciprocal juxtamembrane steric clashes.

Characterization of a Plasmodium falciparum PHISTc protein, PF3D7_0801000, in blood- stage malaria parasites

November 7, 2020 - 12:38 -- Open Access
Nagaoka H, Kanoi BN, Morita M, Nakata T, Palacpac NMQ, Egwang TG, Horii T, Tsuboi T, Takashima E
Parasitol Int. 2020 Nov 1:102240

During intraerythrocytic development Plasmodium falciparum deploys numerous proteins to support erythrocyte invasion, intracellular growth and development, as well as host immune evasion. Since these proteins are key for parasite intraerythrocytic survival and propagation, they represent attractive targets for antimalarial vaccines. In this study we sought to characterize a member of the PHISTc family of proteins, PF3D7_0801000, as a potential vaccine target.

A comprehensive RNA handling and transcriptomics guide for high-throughput processing of Plasmodium blood-stage samples

October 13, 2020 - 12:36 -- Open Access
Michal Kucharski, Jaishree Tripathi, Sourav Nayak, Lei Zhu, Grennady Wirjanata, Rob W. van der Pluijm, Mehul Dhorda, Arjen Dondorp and Zbynek Bozdech
Malaria Journal 2020 19:363, 9 October 2020

Sequencing technology advancements opened new opportunities to use transcriptomics for studying malaria pathology and epidemiology. Even though in recent years the study of whole parasite transcriptome proved to be essential in understanding parasite biology there is no compiled up-to-date reference protocol for the efficient generation of transcriptome data from growing number of samples. Here, a comprehensive methodology on how to preserve, extract, amplify, and sequence full-length mRNA transcripts from Plasmodium-infected blood samples is presented that can be fully streamlined for high-throughput studies.

NOT Open Access | First-in-human randomised trial and follow-up study of Plasmodium falciparum blood-stage malaria vaccine BK-SE36 with CpG-ODN(K3)

October 7, 2020 - 14:28 -- NOT Open Access
Ezoe S, Palacpac NMQ, Horii T, et al.
Vaccine. 2020 Oct 1:S0264-410X(20)31227-5

BK-SE36 is blood-stage malaria vaccine candidate that is undergoing clinical trials. Here, the safety and immunogenicity of BK-SE36 with a novel adjuvant, CpG-ODN(K3) (thus, BK-SE36/CpG) was assessed in a phase 1a trial in Japan.

The Structure of the Cysteine-Rich Domain of Plasmodium falciparum P113 Identifies the Location of the RH5 Binding Site

September 10, 2020 - 08:42 -- Open Access
Campeotto I, Galaway F, Mehmood S, Barfod LK, Quinkert D, Kotraiah V, Phares TW, Wright KE, Snijders AP, Draper SJ, Higgins MK, Wright GJ
mBio. 2020 Sep 8;11(5):e01566-20

Plasmodium falciparum RH5 is a secreted parasite ligand that is essential for erythrocyte invasion through direct interaction with the host erythrocyte receptor basigin. RH5 forms a tripartite complex with two other secreted parasite proteins, CyRPA and RIPR, and is tethered to the surface of the parasite through membrane-anchored P113. Antibodies against RH5, CyRPA, and RIPR can inhibit parasite invasion, suggesting that vaccines containing these three components have the potential to prevent blood-stage malaria.

NOT Open Access | Designing a multi-epitope vaccine against blood-stage of Plasmodium falciparum by in silico approaches

September 5, 2020 - 15:59 -- NOT Open Access
Bemani P, Amirghofran Z, Mohammadi M
J Mol Graph Model. 2020 Sep;99:107645

Plasmodium falciparum causes the most severe form of malaria disease and is the major cause of infection-related mortalities in the world. Due to increasing in P. falciparum resistance to the first-line antimalarial drugs, an effective vaccine for the control and elimination of malaria infection is urgent. Because the pathogenesis of malaria disease results from blood-stage infection, and all of the symptoms and clinical illness of malaria occur during this stage, there is a strong rationale to develop vaccine against this stage.

Safety, tolerability, pharmacokinetics, and antimalarial efficacy of a novel Plasmodium falciparum ATP4 inhibitor SJ733: a first-in-human and induced blood-stage malaria phase 1a/b trial

August 3, 2020 - 15:49 -- Open Access
Gaur AH, McCarthy JS, Panetta JC, Dallas RH, Woodford J, Tang L, Smith AM, Stewart TB, Branum KC, Freeman BB 3rd, Patel ND, John E, Chalon S, Ost S, Heine RN, Richardson JL, Christensen R, Flynn PM, Van Gessel Y, Mitasev B, Möhrle JJ, Gusovsky F, Bebrevska L, Guy RK
Lancet Infect Dis. 2020 Aug; 20(8):964-975

(+)-SJ000557733 (SJ733) is a novel, orally bioavailable inhibitor of Plasmodium falciparum ATP4. In this first-in-human and induced blood-stage malaria phase 1a/b trial, we investigated the safety, tolerability, pharmacokinetics, and antimalarial activity of SJ733 in humans.

Antimalarial activity of artefenomel against asexual parasites and transmissible gametocytes during experimental blood-stage Plasmodium vivax infection

June 2, 2020 - 09:34 -- Open Access
Collins KA, Abd-Rahman AN, Marquart L, Ballard E, Gobeau N, Griffin P, Chalon S, Möhrle JJ, McCarthy JS
J Infect Dis. 2020 Jun 1:jiaa287

Interventions that effectively target Plasmodium vivax are critical for the future control and elimination of malaria. We conducted a P. vivax volunteer infection study to characterise the antimalarial activity of artefenomel, a new drug candidate.


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