The Need for Novel Asexual Blood-Stage Malaria Vaccine Candidates for Plasmodium falciparum.

Extensive control efforts have significantly reduced malaria cases and deaths over the past two decades, but in recent years, coupled with the COVID-19 pandemic, success has stalled. The WHO has urged the implementation of a number of interventions, including vaccines. The modestly effective RTS,S/AS01 pre-erythrocytic vaccine has been recommended by the WHO for use in sub-Saharan Africa against Plasmodium falciparum in children residing in moderate to high malaria transmission regions. A second pre-erythrocytic vaccine, R21/Matrix-M, was also recommended by the WHO on 3 October 2023. However, the paucity and limitations of pre-erythrocytic vaccines highlight the need for asexual blood-stage malaria vaccines that prevent disease caused by blood-stage parasites. Few asexual blood-stage vaccine candidates have reached phase 2 clinical development, and the challenges in terms of their efficacy include antigen polymorphisms and low immunogenicity in humans. This review summarizes the history and progress of asexual blood-stage malaria vaccine development, highlighting the need for novel candidate vaccine antigens/molecules.

High-Throughput Antibody Profiling Identifies Targets of Protective Immunity against P. falciparum Malaria in Thailand.

Malaria poses a significant global health challenge, resulting in approximately 600,000 deaths each year. Individuals living in regions with endemic malaria have the potential to develop partial immunity, thanks in part to the presence of anti-plasmodium antibodies. As efforts are made to optimize and implement strategies to reduce malaria transmission and ultimately eliminate the disease, it is crucial to understand how these interventions impact naturally acquired protective immunity. To shed light on this, our study focused on assessing antibody responses to a carefully curated library of P. falciparum recombinant proteins (n = 691) using samples collected from individuals residing in a low-malaria-transmission region of Thailand. We conducted the antibody assays using the AlphaScreen system, a high-throughput homogeneous proximity-based bead assay that detects protein interactions. We observed that out of the 691 variable surface and merozoite stage proteins included in the library, antibodies to 268 antigens significantly correlated with the absence of symptomatic malaria in an univariate analysis. Notably, the most prominent antigens identified were P. falciparum erythrocyte membrane protein 1 (PfEMP1) domains. These results align with our previous research conducted in Uganda, suggesting that similar antigens like PfEMP1s might play a pivotal role in determining infection outcomes in diverse populations. To further our understanding, it remains critical to conduct functional characterization of these identified proteins, exploring their potential as correlates of protection or as targets for vaccine development.

Co-encapsulation of multivitamins in micro & nano-sized starch, target release, capsule characterization and interaction studies.

This study aims to protect sensitive vitamins D, E, B1 and B2 by co-encapsulation in micro and nanoparticles of water chestnut starch for synergistic effects. The encapsulation efficiency, particle size, thermal properties and molecular configuration & interactions studies were analysed. The nano-sized starch with a particle size of 362 nm showed better encapsulation potential than micro-sized starch having an average particle size of 3.47 µm. The encapsulation efficiency was found to be 35 %, 81.17 %, 83.13 %, & 76.07 % and 46.27 %, 89.29 %, 84.91 %, & 77.60 % for vitamin D, E, B1 and B2 in micro and nano-sized starch, respectively. Fluorescence spectroscopy showed higher intensity for non-covalent interactions within the internal matrix of capsules. The FTIR peak at 877 cm-1 belonging to vitamin ring structures was prominent and confirmed the presence of vitamins in encapsulated powders. The nano starch capsules of vitamins showed better thermal stability with low crystallinity than micro starch capsules of vitamins. The study suggests the use of co-encapsulated vitamins in food fortification/supplementation to overcome the issues related to vitamin deficiencies.

Extraction of polysaccharide from Althea rosea and its physicochemical, anti-diabetic, anti-hypertensive and antioxidant properties.

The valorization of new polymer sources from underutilized plants as structuring, encapsulating, and texturizing agents for food and nutraceutical applications is gaining attention. This provides an opportunity where inexpensive plant-sourced biopolymers can play an impactful role, on both ecological and economic aspects performing equivalently effectual yet cost-effective substitutes to synthetic polymers. With this aim, we explored the use of mucilage from Althea rosea and reveal its physicochemical, in vitro antidiabetic and antihypertensive activity. Besides, structural, micrometric, crystallization, and anti-microbial properties was also seen. We determined the probable structure of the extracted mucilage by FTIR which confirmed the residues of saccharides as galactose and uronic acid with α and ß configurations. It consists of 78.26% carbohydrates, 3.51% ashes, and 3.72% proteins. Here, we show that the mucilage offered protection to DNA against the oxidative damage caused by (-OH) radicals and the morphology of the mucilage particles displayed a fibrillary material settled in a net-like, tangled structure. Our results demonstrate that the reconstituted mucilage powder exhibited good water holding capacity (2.89 g water/g mucilage), solubility (27.33%), and oil holding capacity (1.79 g oil/g mucilage). Moreover, high emulsifying property (95.83%) and foaming capacity (17.04%) was noted. Our results indicate that A.rosea mucilage can potentially serve as economical and eco-friendly hydrocolloid substitute for the food and nutraceutical industry owing to its functional, hypo-lipidemic, anti-hyperglycemic, antioxidant, and anti-bacterial properties.

Meta-Analysis of Human Antibodies Against Plasmodium falciparum Variable Surface and Merozoite Stage Antigens.

Concerted efforts to fight malaria have caused significant reductions in global malaria cases and mortality. Sustaining this will be critical to avoid rebound and outbreaks of seasonal malaria. Identifying predictive attributes that define clinical malaria will be key to guide development of second-generation tools to fight malaria. Broadly reactive antibodies against variable surface antigens that are expressed on the surface of infected erythrocytes and merozoites stage antigens are targets of naturally acquired immunity and prime candidates for anti-malaria therapeutics and vaccines. However, predicting the relationship between the antigen-specific antibodies and protection from clinical malaria remains unresolved. Here, we used new datasets and multiple approaches combined with re-analysis of our previous data to assess the multi-dimensional and complex relationship between antibody responses and clinical malaria outcomes. We observed 22 antigens (17 PfEMP1 domains, 3 RIFIN family members, merozoite surface protein 3 (PF3D7_1035400), and merozoites-associated armadillo repeats protein (PF3D7_1035900) that were selected across three different clinical malaria definitions (1,000/2,500/5,000 parasites/µl plus fever). In addition, Principal Components Analysis (PCA) indicated that the first three components (Dim1, Dim2 and Dim3 with eigenvalues of 306, 48, and 29, respectively) accounted for 66.1% of the total variations seen. Specifically, the Dim1, Dim2 and Dim3 explained 52.8%, 8.2% and 5% of variability, respectively. We further observed a significant relationship between the first component scores and age with antibodies to PfEMP1 domains being the key contributing variables. This is consistent with a recent proposal suggesting that there is an ordered acquisition of antibodies targeting PfEMP1 proteins. Thus, although limited, and further work on the significance of the selected antigens will be required, these approaches may provide insights for identification of drivers of naturally acquired protective immunity as well as guide development of additional tools for malaria elimination and eradication.

Production and characterization of starch nanoparticles by mild alkali hydrolysis and ultra-sonication process.

In this report, synthesis of the starch nanoparticles from underutilized and cheap sources viz: Horse chestnut (HS), Water chestnut (WS) and Lotus stem (LS) by using mild alkali hydrolysis and ultra-sonication process has been presented. The particles were characterized by Differential scanning colorimeter (DSC), X-Ray Diffraction (XRD), Rheology, Scanning electron microscopy (SEM) and Fourier transform infra-spectroscopy (ATR-FTIR). The particle size measurements, functional properties and antioxidant potential of starch nanoparticles were also analyzed. The experimental results revealed that the average particle size diameter of Horse chestnut starch nanoparticles (HSP), Water chestnut starch nanoparticles (WSP) and Lotus stem starch nanoparticles (LSP) was found to be 420, 606 and 535 nm, respectively. We observed a notable increase in the water absorption capacity but decreased capacity for oil absorption in the starch nano-particles. SEM images revealed damaged starch granules after size reduction. Additionally, loss of crystallinity and molecular order was observed from XRD and ATR-FTIR spectra. It was concluded that the starch nanoparticles have better thermal stability, increased viscosity and antioxidant properties.