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Safety, infectivity and immunogenicity of a genetically attenuated blood-stage malaria vaccine

November 25, 2021 - 13:03 -- Open Access
Webster R, Sekuloski S, McCarthy JS, et al.
BMC Med. 2021 Nov 22;19(1):293

There is a clear need for novel approaches to malaria vaccine development. We aimed to develop a genetically attenuated blood-stage vaccine and test its safety, infectivity, and immunogenicity in healthy volunteers. Our approach was to target the gene encoding the knob-associated histidine-rich protein (KAHRP), which is responsible for the assembly of knob structures at the infected erythrocyte surface. Knobs are required for correct display of the polymorphic adhesion ligand P. falciparum erythrocyte membrane protein 1 (PfEMP1), a key virulence determinant encoded by a repertoire of var genes.

Population genetic analysis of the Plasmodium falciparum erythrocyte binding antigen-175 (EBA-175) gene in Equatorial Guinea

October 6, 2021 - 20:04 -- Open Access
Pei-Kui Yang, Xue-Yan Liang, Ying-E. Wu, et al.
Malaria Journal 2021 20:374, 19 September 2021

Plasmodium falciparum erythrocyte binding antigen-175 (PfEBA-175) is a candidate antigen for a blood-stage malaria vaccine, while various polymorphisms and dimorphism have prevented to development of effective vaccines based on this gene. This study aimed to investigate the dimorphism of PfEBA-175 on both the Bioko Island and continent of Equatorial Guinea, as well as the genetic polymorphism and natural selection of global PfEBA-175.

Not Open Access | Memory CD8(+) T cells exhibit tissue imprinting and non-stable exposure-dependent reactivation characteristics following blood-stage Plasmodium berghei ANKA infections

August 25, 2021 - 15:48 -- NOT Open Access
Shaw TN, Haley MJ, Dookie RS, Godfrey JJ, Cheeseman AJ, Strangward P, Zeef LAH, Villegas-Mendez A, Couper KN
Immunology. 2021 Aug 18

Experimental cerebral malaria (ECM) is a severe complication of Plasmodium berghei ANKA (PbA) infection in mice, characterised by CD8+ T cell accumulation within the brain. Whilst the dynamics of CD8+ T cell activation and migration during extant primary PbA infection have been extensively researched, the fate of the parasite-specific CD8+ T cells upon resolution of ECM are not understood. In this study we show that memory OT-I cells persist systemically within the spleen, lung and brain following recovery from ECM after primary PbA-OVA infection.

Sequence analysis of Plasmodium vivax Duffy binding proteins reveals the presence of unique haplotypes and diversifying selection in Ethiopian isolates

July 14, 2021 - 11:10 -- Open Access
Lemu Golassa, Alebachew Messele, Eniyou Cheryll Oriero and Alfred Amambua-Ngwa
Malaria Journal 2021 20:312, 10 July 2021

Red blood cell invasion by the Plasmodium vivax merozoite requires interaction between the Duffy antigen receptor for chemokines (DARC) and the P. vivax Duffy-binding protein II (PvDBPII). Given that the disruption of this interaction prevents P. vivax blood-stage infection, a PvDBP-based vaccine development has been well recognized. However, the polymorphic nature of PvDBPII prevents a strain transcending immune response and complicates attempts to design a vaccine.

Using Plasmodium knowlesi as a model for screening Plasmodium vivax blood-stage malaria vaccine targets reveals new candidates

July 6, 2021 - 14:38 -- Open Access
Ndegwa DN, Kundu P, Hostetler JB, Marin-Menendez A, Sanderson T, Mwikali K, Verzier LH, Coyle R, Adjalley S, Rayner JC
PLoS Pathog. 2021 Jul 1;17(7):e1008864

Plasmodium vivax is responsible for the majority of malaria cases outside Africa. Unlike P. falciparum, the P. vivax life-cycle includes a dormant liver stage, the hypnozoite, which can cause infection in the absence of mosquito transmission. An effective vaccine against P. vivax blood stages would limit symptoms and pathology from such recurrent infections, and therefore could play a critical role in the control of this species. Vaccine development in P. vivax, however, lags considerably behind P. falciparum, which has many identified targets with several having transitioned to Phase II testing.

NOT Open Access | Immunogenicity and structural efficacy of P41 of Plasmodium sp. as potential cross-species blood-stage malaria vaccine

June 9, 2021 - 14:14 -- NOT Open Access
Ramanto KN, Nurdiansyah R
Comput Biol Chem. 2021 Jun;92:107493

Vaccine based strategies offer a promising future in malaria control by generating protective immunity against natural infection. However, vaccine development is hindered by the Plasmodium sp. genetic diversity. Previously, we have shown P41 protein from 6-Cysteine shared by Plasmodium sp. and could be used for cross-species anti-malaria vaccines.

Exploratory analysis of the effect of helminth infection on the immunogenicity and efficacy of the asexual blood-stage malaria vaccine candidate GMZ2

June 8, 2021 - 10:50 -- Open Access
Nouatin O, Mengue JB, Adegnika AA, et al.
PLoS Negl Trop Dis. 2021 Jun 1;15(6):e0009361

Helminths can modulate the host immune response to Plasmodium falciparum and can therefore affect the risk of clinical malaria. We assessed here the effect of helminth infections on both the immunogenicity and efficacy of the GMZ2 malaria vaccine candidate, a recombinant protein consisting of conserved domains of GLURP and MSP3, two asexual blood-stage antigens of P. falciparum. Controlled human malaria infection (CHMI) was used to assess the efficacy of the vaccine.

Shifts in Gene Expression Variability in the blood-stage of Plasmodium relictum

May 26, 2021 - 14:43 -- Open Access
Kalbskopf V, Ahrén D, Valkiūnas G, Palinauskas V, Hellgren O
Gene. 2021 May 18:145723

Avian malaria is a common and widespread disease of birds caused by a diverse group of pathogens of the genera Plasmodium. We investigated the transcriptomal profiles of one of the most common species, Plasmodium relictum, lineage SGS1, at multiple timepoints during the blood stages of the infection under experimental settings.

MAIP: a web service for predicting blood-stage malaria inhibitors

February 25, 2021 - 08:15 -- Open Access
Bosc N, Felix E, Leach AR, et al.
J Cheminform. 2021 Feb 22;13(1):13

Malaria is a disease affecting hundreds of millions of people across the world, mainly in developing countries and especially in sub-Saharan Africa. It is the cause of hundreds of thousands of deaths each year and there is an ever-present need to identify and develop effective new therapies to tackle the disease and overcome increasing drug resistance. Here, we extend a previous study in which a number of partners collaborated to develop a consensus in silico model that can be used to identify novel molecules that may have antimalarial properties.

NOT Open Access | Host-pathogen interaction in the tissue environment during Plasmodium blood-stage infection

February 3, 2021 - 15:11 -- NOT Open Access
Yui K, Inoue SI
Parasite Immunol. 2021 Feb;43(2):e12763

Human malarial infection occurs after an infectious Anopheles mosquito bites. Following the initial liver-stage infection, parasites transform into merozoites, infecting red blood cells (RBCs). Repeated RBC infection then occurs during the blood-stage infection, while patients experience various malarial symptoms. Protective immune responses are elicited by this systemic infection, but excessive responses are sometimes harmful for hosts.


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