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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.

Immune system challenge improves recognition memory and reverses malaria-induced cognitive impairment in mice

July 28, 2021 - 13:00 -- Open Access
de Sousa LP, Ribeiro-Gomes FL, de Almeida RF, Souza TME, Werneck GL, Souza DO, Daniel-Ribeiro CT
Sci Rep. 2021 Jul 21;11(1):14857

The immune system plays a role in the maintenance of healthy neurocognitive function. Different patterns of immune response triggered by distinct stimuli may affect nervous functions through regulatory or deregulatory signals, depending on the properties of the exogenous immunogens. Here, we investigate the effect of immune stimulation on cognitive-behavioural parameters in healthy mice and its impact on cognitive sequelae resulting from non-severe experimental malaria.

Messenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice

June 22, 2021 - 15:09 -- Open Access
Mallory KL, Taylor JA, Angov E, et al.
NPJ Vaccines. 2021 Jun 18;6(1):84

Human malaria affects the vast majority of the world's population with the Plasmodium falciparum species causing the highest rates of morbidity and mortality. With no licensed vaccine and leading candidates achieving suboptimal protection in the field, the need for an effective immunoprophylactic option continues to motivate the malaria research community to explore alternative technologies. Recent advances in the mRNA discipline have elevated the long-neglected platform to the forefront of infectious disease research.

The power and promise of genetic mapping from Plasmodium falciparum crosses utilizing human liver-chimeric mice

June 16, 2021 - 15:12 -- Open Access
Button-Simons KA, Kumar S, Cheeseman IH, et al.
Commun Biol. 2021 Jun 14;4(1):734

Genetic crosses are most powerful for linkage analysis when progeny numbers are high, parental alleles segregate evenly and numbers of inbred progeny are minimized. We previously developed a novel genetic crossing platform for the human malaria parasite Plasmodium falciparum, an obligately sexual, hermaphroditic protozoan, using mice carrying human hepatocytes (the human liver-chimeric FRG NOD huHep mouse) as the vertebrate host. We report on two genetic crosses-(1) an allopatric cross between a laboratory-adapted parasite (NF54) of African origin and a recently patient-derived Asian parasite, and (2) a sympatric cross between two recently patient-derived Asian parasites.

Analysis of spleen histopathology, splenocyte composition and haematological parameters in four strains of mice infected with Plasmodium berghei K173

June 9, 2021 - 07:42 -- Open Access
Huajing Wang, Shuo Li, Zhao Cui, Tingting Qin, Hang Shi, Ji Ma, Lanfang Li, Guihua Yu, Tingliang Jiang and Canghai Li
Malaria Journal 2021 20:249, 6 June 2021

Malaria is a fatal disease that presents clinically as a continuum of symptoms and severity, which are determined by complex host-parasite interactions. Clearance of infection is believed to be accomplished by the spleen and mononuclear phagocytic system (MPS), independent of artemisinin treatment. The spleen filters infected red blood cells (RBCs) from circulation through immune-mediated recognition of the infected RBCs followed by phagocytosis. This study evaluated the tolerance of four different strains of mice to Plasmodium berghei strain K173 (P. berghei K173), and the differences in the role of the spleen in controlling P. berghei K173 infection.

Ultra-low dose immunization and multi-component vaccination strategies enhance protection against malaria in mice

May 26, 2021 - 09:37 -- Open Access
Collins KA, Brod F, Snaith R, Ulaszewska M, Longley RJ, Salman AM, Gilbert SC, Spencer AJ, Franco D, Ballou WR, Hill AVS
Sci Rep. 2021 May 24;11(1):10792

An effective vaccine would be a valuable tool for malaria control and elimination; however, the leading malaria vaccine in development, RTS,S/AS01, provided only partial protection in a Phase 3 trial. R21 is a next-generation RTS,S-like vaccine. We have previously shown in mice that R21 administered in Matrix-M is highly immunogenic, able to elicit complete protection against sporozoite challenge, and can be successfully administered with TRAP based viral-vectors resulting in enhanced protection. In this study, we developed a novel, GMP-compatible purification process for R21, and evaluated the immunogenicity and protective efficacy of ultra-low doses of both R21 and RTS,S when formulated in AS01.

NOT Open Access | Artemether and lumefantrine dissolving microneedle patches with improved pharmacokinetic performance and antimalarial efficacy in mice infected with Plasmodium yoelii

May 19, 2021 - 15:26 -- NOT Open Access
Volpe-Zanutto F, Ferreira LT, Foglio MA, et al.
J Control Release. 2021 May 10;333:298-315

Malaria affects more than 200 million people annually around the world, killing a child every 2 min. Artemether (ART) and lumefantrine (LUM) are the gold standard choice to treat uncomplicated Plasmodium falciparum malaria; however, they are hydrophobic compounds with low oral bioavailability. Microneedle (MN) arrays consist of micron-sized needles on one side of a supporting base and have the ability to bypass the skin's stratum corneum barrier in a minimally invasive way, creating temporary channels through which drugs can diffuse, including those with poor water solubility.

NOT Open Access | Phytol suppresses parasitemia and ameliorates anaemia and oxidative brain damage in mice infected with Plasmodium berghei

May 5, 2021 - 11:01 -- NOT Open Access
Usman MA, Usman FI, Abubakar MS, Salman AA, Adamu A, Ibrahim MA
Exp Parasitol. 2021 May;224:108097

The quest for the development of a novel antimalarial drug informed the decision to subject phytol to in vivo trials following a demonstration of therapeutic potential against chloroquine sensitive strain of Plasmodium falciparum under in vitro condition. On this basis, the in vivo anti-Plasmodium berghei activity of phytol including the ameliorative effects of the compound on P. berghei-associated anaemia and organ damage were investigated.

Studies on the mitochondrial, immunological and inflammatory effects of solvent fractions of Diospyros mespiliformis Hochst in Plasmodium berghei-infected mice

March 30, 2021 - 14:28 -- Open Access
David OM, Olanlokun JO, Owoniyi BE, Ayeni M, Ebenezer O, Koorbanally NA
Sci Rep. 2021 Mar 25;11(1):6941

The use of medicinal plants in the treatment of malaria is gaining global attention due to their efficacy and cost effectiveness. This study evaluated the bioactivity-guided antiplasmodial efficacy and immunomodulatory effects of solvent fractions of Diospyros mespiliformis in mice infected with a susceptible strain of Plasmodium berghei (NK 65). The crude methanol extract of the stem of D. mespiliformis (DM) was partitioned between n-hexane, dichloromethane, ethyl acetate and methanol. Male Swiss mice (20 ± 2 g) infected with P. berghei were grouped and treated with vehicle (10 mL/kg, control), Artemether lumefantrine (10 mg/kg), 100, 200 and 400 mg/kg of n-hexane, dichloromethane, ethyl acetate and methanol fractions of D. mespiliformis for seven days. Blood was obtained for heme and hemozoin contents while serum was obtained for inflammatory cytokines and immunoglobulins G and M assessments.

Adipose tissue parasite sequestration drives leptin production in mice and correlates with human cerebral malaria

March 26, 2021 - 16:05 -- Open Access
Mejia P, Treviño-Villarreal JH, Mitchell JR, et al.
Sci Adv. 2021 Mar 24;7(13):eabe2484

Circulating levels of the adipokine leptin are linked to neuropathology in experimental cerebral malaria (ECM), but its source and regulation mechanism remain unknown. Here, we show that sequestration of infected red blood cells (iRBCs) in white adipose tissue (WAT) microvasculature increased local vascular permeability and leptin production. Mice infected with parasite strains that fail to sequester in WAT displayed reduced leptin production and protection from ECM.


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