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Population genetic and biophysical evidences reveal that purifying selection shapes the genetic landscape of Plasmodium falciparum RH ligands in Chhattisgarh and West Bengal, India

October 15, 2020 - 08:19 -- Open Access
Sharmistha Ghoshal, Pramita Chowdhury, Sanhita Ray, Mitashree Mitra, Sumana Datta Kanjilal, Srikanta Sen, Anjan Kr. Dasgupta and Sanghamitra Sengupta
Malaria Journal 2020 19:367,14 October 2020

Reticulocyte binding protein-like homologs (RHs) are currently being evaluated as anti-erythrocytic stage vaccine targets against Plasmodium falciparum malaria. Present study explores the possible evolutionary drivers shaping the genetic organization of Pfrhs in Indian parasite population. It simultaneously evaluates a putative gain-of-function variant of PfRH5, a keystone member of PfRH family.

NOT Open Access | The use of proteomics for the identification of promising vaccine and diagnostic biomarkers in Plasmodium falciparum

October 1, 2020 - 07:52 -- NOT Open Access
Mansouri R, Ali-Hassanzadeh M, Shafiei R, Savardashtaki A, Karimazar M, Anvari E, Nguewa P, Rashidi S
Parasitology. 2020 Oct;147(12):1255-1262

Plasmodium falciparum is the main cause of severe malaria in humans that can lead to death. There is growing evidence of drug-resistance in P. falciparum treatment, and the design of effective vaccines remains an ongoing strategy to control the disease. On the other hand, the recognition of specific diagnostic markers for P. falciparum can accelerate the diagnosis of this parasite in the early stages of infection.

NOT Open Access | Red blood cell tension protects against severe malaria in the Dantu blood group

September 23, 2020 - 09:23 -- NOT Open Access
Kariuki SN, Marin-Menendez A, Rayner JC, et al.
Nature. 2020 Sep 16

Malaria has had a major effect on the human genome, with many protective polymorphisms-such as the sickle-cell trait-having been selected to high frequencies in malaria-endemic regions1,2. The blood group variant Dantu provides 74% protection against all forms of severe malaria in homozygous individuals3-5, a similar degree of protection to that afforded by the sickle-cell trait and considerably greater than that offered by the best malaria vaccine.

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 | Measuring of IgG2c isotype instead of IgG2a in immunized C57BL/6 mice with Plasmodium vivax TRAP as a subunit vaccine candidate in order to correct interpretation of Th1 versus Th2 immune response

September 5, 2020 - 15:36 -- NOT Open Access
Nazeri S, Zakeri S, Mehrizi AA, Sardari S, Djadid ND
Exp Parasitol. 2020 Sep;216:107944

Evaluation of the murine isotype antibodies is essential in subunit vaccine development because inbred mouse strains with diverse genetic backgrounds respond different to recombinant proteins. In this regard, the main goal of this study was to measuring and comparing the profile of IgG isotype responses in C57BL/6 mice. For this purpose, the extracellular region of plasmodium vivax thrombospondin-related adhesive protein (PvTRAP) gene was expressed in Escherichia coli Rosetta (DE3)-pET23a.

NOT Open Access | An AMA1/MSP1(19) Adjuvanted Malaria Transplastomic Plant-Based Vaccine Induces Immune Responses in Test Animals

September 2, 2020 - 08:37 -- NOT Open Access
Milán-Noris EM, Monreal-Escalante E, Rosales-Mendoza S, Soria-Guerra RE, Radwan O, Juvik JA, Korban SS
Mol Biotechnol. 2020 Sep 1

Malaria is a tropical human disease, caused by protozoan parasites, wherein a significant number of the world's population is at risk. Annually, more than 219 million new cases are reported. Although there are prevention treatments, there are no highly and widely effective licensed anti-malarial vaccines available for use. Opportunities for utilization of plant-based vaccines as novel platforms for developing safe, reliable, and affordable treatments offer promise for developing such a vaccine against malaria.

Quantification of Plasmodium knowlesi versus Plasmodium falciparum in the rhesus liver: implications for malaria vaccine studies in rhesus models

September 1, 2020 - 10:12 -- Open Access
Melanie J. Shears, Annette M. Seilie, B. Kim Lee Sim, Stephen L. Hoffman and Sean C. Murphy
Malaria Journal 2020 19:313, 31 August 2020

Rhesus macaques are valuable pre-clinical models for malaria vaccine development. The Plasmodium knowlesi/rhesus and Plasmodium falciparum/rhesus models are two established platforms for malaria vaccine testing, and both have previously been used to assess live-attenuated sporozoite vaccines. However, there is evidence that the susceptibility of the rhesus liver to P. knowlesi versus P. falciparum sporozoites likely differs, potentially complicating comparisons between these two platforms.

NOT Open Access | Communities and Clinical Trials: A Case Study from the RTS,S Malaria Vaccine Trials in Eastern Africa

August 31, 2020 - 15:06 -- NOT Open Access
Wyss-van den Berg M, Ogutu B, Sewankambo NK, Merten S, Biller-Andorno N, Tanner M
J Empir Res Hum Res Ethics. 2020 Aug 26:1556264620951384

When clinical trials enter human communities, two complex systems merge-creating challenges for the clinical trial team and the local human community. This is of particular relevance for clinical trials in low-resource settings where the resource scarcity can intensify existing inequities. Here we present a case study of a phase III malaria vaccine clinical trial.

NOT Open Access | Virus-like particles expressing Plasmodium berghei MSP-8 induce protection against P. berghei infection

August 5, 2020 - 14:10 -- NOT Open Access
Lee SH, Chu KB, Kang HJ, Basak S, Kim MJ, Park H, Jin H, Moon EK, Quan FS
Parasite Immunol. 2020 Aug 1:e12781

Merozoite surface protein 8 (MSP‐8) of Plasmodium parasites play an important role in erythrocyte invasion and is a potential malaria vaccine candidate.

Structure and function of a malaria transmission blocking vaccine targeting Pfs230 and Pfs230-Pfs48/45 proteins

July 27, 2020 - 15:01 -- Open Access
Singh K, Burkhardt M, Narum DL, et al.
Commun Biol. 2020 Jul 24;3(1):395

Proteins Pfs230 and Pfs48/45 are Plasmodium falciparum transmission-blocking (TB) vaccine candidates that form a membrane-bound protein complex on gametes. The biological role of Pfs230 or the Pfs230-Pfs48/45 complex remains poorly understood. Here, we present the crystal structure of recombinant Pfs230 domain 1 (Pfs230D1M), a 6-cysteine domain, in complex with the Fab fragment of a TB monoclonal antibody (mAb) 4F12. We observed the arrangement of Pfs230 on the surface of macrogametes differed from that on microgametes, and that Pfs230, with no known membrane anchor, may exist on the membrane surface in the absence of Pfs48/45.


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