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Scientific Articles

A C-terminal Pfs48/45 malaria transmission-blocking vaccine candidate produced in the baculovirus expression system

February 2, 2020 - 17:28 -- Open Access
Shwu-Maan Lee, John M. Hickey, Kazutoyo Miura, Sangeeta B. Joshi, David B. Volkin, C. Richter King, Jordan L. Plieskatt
Scientific Reports volume 10:395 (2020)

The Plasmodium falciparum gametocyte surface protein, Pfs48/45, is a potential target for malaria transmission-blocking vaccines. However, due to its size and complexity, expression of the full-length protein has been difficult, leading to focus on the C-terminal six cysteine domain (6C) with the use of fusion proteins to facilitate expression and folding. In this study, we utilized the baculovirus system to evaluate the expression of three Pfs48/45 proteins including the full-length protein, the 6C domain fragment and the 6C domain mutant to prevent glycosylation.

The mosquito electrocuting trap as an exposure-free method for measuring human-biting rates by Aedes mosquito vectors

February 2, 2020 - 17:23 -- Open Access
Leonardo D. Ortega-López, Emilie Pondeville, Alain Kohl, Renato León, Mauro Pazmiño Betancourth, Floriane Almire, Sergio Torres-Valencia, Segundo Saldarriaga, Nosrat Mirzai, Heather M. Ferguson
Parasites Vectors 2020; 13:31

Entomological monitoring of Aedes vectors has largely relied on surveillance of larvae, pupae and non-host-seeking adults, which have been poorly correlated with human disease incidence. Exposure to mosquito-borne diseases can be more directly estimated using human landing catches (HLC), although this method is not recommended for Aedes-borne arboviruses. We evaluated a new method previously tested with malaria vectors, the mosquito electrocuting trap (MET) as an exposure-free alternative for measuring landing rates of Aedes mosquitoes on people. Aims were to (i) compare the MET to the BG-sentinel (BGS) trap gold standard approach for sampling host-seeking Aedes vectors; and (ii) characterize the diel activity of Aedes vectors and their association with microclimatic conditions.

Attenuation of TCR-induced transcription by Bach2 controls regulatory T cell differentiation and homeostasis

January 31, 2020 - 16:17 -- Open Access
Tom Sidwell, Yang Liao, Axel Kallies, et al.
Nature Communications volume 11, Article number: 252 (2020)

Differentiation and homeostasis of Foxp3+ regulatory T (Treg) cells are strictly controlled by T-cell receptor (TCR) signals; however, molecular mechanisms that govern these processes are incompletely understood. Here we show that Bach2 is an important regulator of Treg cell differentiation and homeostasis downstream of TCR signaling. Bach2 prevents premature differentiation of fully suppressive effector Treg (eTreg) cells, limits IL-10 production and is required for the development of peripherally induced Treg (pTreg) cells in the gastrointestinal tract.

Gut microbiota is essential in PGRP-LA regulated immune protection against Plasmodium berghei infection

January 27, 2020 - 16:06 -- Open Access
Gao L, Song X, Wang J
Parasites & Vectors, 2020 Jan 6; 13(1):3.

Malaria remains to be one of the deadliest infectious diseases and imposes substantial financial and social costs in the world. Mosquitoes rely on the immune system to control parasite infection. Peptidoglycan recognition proteins (PGRPs), a family of pattern-recognition receptors (PRR), are responsible for initiating and regulating immune signaling pathways. PGRP-LA is involved in the regulation of immune defense against the Plasmodium parasite, however, the underlying mechanism needs to be further elucidated.

Preclinical Development and Assessment of Viral Vectors Expressing a Fusion Antigen of Plasmodium falciparum LSA1 and LSAP2 for Efficacy against Liver-Stage Malaria

January 27, 2020 - 13:52 -- Open Access
Benedict R. Halbroth, Sarah Sebastian, Alexandra J. Spencer, et al.
Infect. Immun. January 2020 88:e00573-19

Despite promising progress in malaria vaccine development in recent years, an efficacious subunit vaccine against Plasmodium falciparum remains to be licensed and deployed. Cell-mediated protection from liver-stage malaria relies on a sufficient number of antigen-specific T cells reaching the liver during the time that parasites are present. A single vaccine expressing two antigens could potentially increase both the size and breadth of the antigen-specific response while halving vaccine production costs.

NOT Open Access | ZBTB7B (ThPOK) Is Required for Pathogenesis of Cerebral Malaria and Protection against Pulmonary Tuberculosis

January 27, 2020 - 13:49 -- NOT Open Access
James M. Kennedy, Anna Georges, Philippe Gros, et al.
Infect. Immun. January 2020 88:e00845-19

We used a genome-wide screen in N-ethyl-N-nitrosourea (ENU)-mutagenized mice to identify genes in which recessive loss-of-function mutations protect against pathological neuroinflammation. We identified an R367Q mutation in the ZBTB7B (ThPOK) protein in which homozygosity causes protection against experimental cerebral malaria (ECM) caused by infection with Plasmodium berghei ANKA. Zbtb7bR367Q homozygous mice show a defect in the lymphoid compartment expressed as severe reduction in the number of single-positive CD4 T cells in the thymus and in the periphery, reduced brain infiltration of proinflammatory leukocytes in P. berghei ANKA-infected mice, and reduced production of proinflammatory cytokines by primary T cells ex vivo and in vivo.

NOT Open Access | Pharmacokinetics and Ex vivo Antimalarial Activity of Artesunate-Amodiaquine plus Methylene Blue in Healthy Volunteers

January 27, 2020 - 13:47 -- NOT Open Access
Anh CX, Chavchich M, Birrell GW, Van Breda K, Travers T, Rowcliffe K, Lord AR, Shanks GD, Edstein MD
Antimicrob Agents Chemother. 2020 Jan 6. pii: AAC.01441-19

High artesunate combination therapy (ACT) treatment failures of Plasmodium falciparum malaria in Southeast Asia has led to triple drug strategies to extend the useful life of ACTs. In this study, we determined whether methylene blue (MB) alters the pharmacokinetics of artesunate-amodiaquine (ASAQ) and enhances the ex vivo antimalarial activity of ASAQ. In an open labelled, randomized cross-over design, a single oral dose of either ASAQ (200 mg AS/540 mg AQ) alone or with MB (325 mg MB) was administered to 15 healthy Vietnamese volunteers. Serial blood samples were collected up to 28 days after dosing.

NOT Open Access | Plasmodium falciparum Clag9-Associated PfRhopH Complex Is Involved in Merozoite Binding to Human Erythrocytes

January 27, 2020 - 13:43 -- NOT Open Access
Bishwanath Kumar Chourasia, Arunaditya Deshmukh, Inderjeet Kaur, Gourab Paul, Ashutosh Panda, Sumit Rathore, Susheel K. Singh, Michael Theisen, Asif Mohmmed and Pawan Malhotra
Infect. Immun. January 2020 88:e00504-19

Cytoadherence-linked asexual gene 9 (Clag9), a conserved Plasmodium protein expressed during the asexual blood stages, is involved in the cytoadherence of infected red blood cells (RBCs) to the endothelial lining of blood vessels. Here, we show that Plasmodium falciparum Clag9 (PfClag9) is a component of the PfClag9-RhopH complex that is involved in merozoite binding to human erythrocytes. To characterize PfClag9, we expressed four fragments of PfClag9, encompassing the entire protein. Immunostaining analysis using anti-PfClag9 antibodies showed expression and localization of PfClag9 at the apical end of the merozoites.

A rapid quality control test to foster the development of the sterile insect technique against Anopheles arabiensis

January 27, 2020 - 13:42 -- Open Access
Nicole J. Culbert, Nanwintoum Séverin Bimbilé Somda, Maiga Hamidou, Dieudonné Diloma Soma, Silvana Caravantes, Thomas Wallner, Mamai Wadaka, Hanano Yamada and Jérémy Bouyer
Malaria Journal 2020 19:44, 23 January 2020

With the fight against malaria reportedly stalling there is an urgent demand for alternative and sustainable control measures. As the sterile insect technique (SIT) edges closer to becoming a viable complementary tool in mosquito control, it will be necessary to find standardized techniques of assessing male quality throughout the production system and post-irradiation handling. Flight ability is known to be a direct marker of insect quality. A new version of the reference International Atomic Energy Agency/Food and Agricultural Organization (IAEA/FAO) flight test device (FTD), modified to measure the flight ability and in turn quality of male Anopheles arabiensis within a 2-h period via a series of verification experiments is presented.

Evaluation of DawaPlus 3.0 and DawaPlus 4.0, deltamethrin–PBO combination nets against pyrethroid-resistant Anopheles culicifacies in experimental huts in India

January 27, 2020 - 13:40 -- Open Access
Kasinathan Gunasekaran, Sudhansu Sekhar Sahu, Tharmalingam Vijayakumar, Swaminathan Subramanian, Manju Rahi and Purushothaman Jambulingam
Malaria Journal 2020 19:43, 23 January 2020

The development of resistance in vectors is one of the major impediments for malaria control. Adding synergists to insecticides has proven to be an alternative choice for controlling resistant mosquitoes. DawaPlus 3.0 and DawaPlus 4.0 are new long-lasting insecticidal nets (LLINs) in which deltamethrin and a synergist, piperonyl butoxide (PBO) are added into filaments and their efficacy was tested against resistant malaria vector, Anopheles culicifacies in experimental huts in India.


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