Acquisition of naturally acquired antibody response to Plasmodium falciparum erythrocyte membrane protein 1-DBLα and differential regulation of IgG subclasses in severe and uncomplicated malaria

Horata, Natharinee; Choowongkomon, Kiattawee; Ratanabunyong, Siriluk; Tongshoob, Jarinee; Khusmith, Srisin

doi:10.1016/j.apjtb.2017.09.017

Cited by 3 publications

(3 citation statements)

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“…The major parasite species responsible for global malaria incidences are P. vivax; the most wide spread (Angrisano and Robinson 2022 ) and P. falciparum (Hermansyah et al 2017 ) the most virulent (Tachibana et al 2022 ). Acquired immunity (Joseph et al 2019 ) which develops after a few episodes of parasite infections is short-lived (Horata et al 2017 ). Vaccine development to boost host immunity, remains elusive hence chemotherapy is the mainstay of malaria control efforts (Dhanawat et al 2009 ).…”

Section: Introductionmentioning

confidence: 99%

Antimalarial activity assay of artesunate-3-chloro-4(4-chlorophenoxy) aniline in vitro and in mice models

et al. 2023

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The global spread of multi-drug resistant P. falciparum , P. vivax , and P. malariae strains and absence of long-term effective vaccine makes chemotherapy the mainstay of malaria control strategies in endemic settings. The Mossman’s assay and the Organization for Economic Co-operation and Development (OECD), 2001 guideline 423, were used to determine the cytotoxicity and acute oral toxicity of a novel hybrid drug, artesunate-3-Chloro-4(4-chlorophenoxy) aniline (ATSA), in vitro and in vivo, respectively. A modified Desjardins method was used to screen for antiplasmodial activity using P. falciparum (3D 7 and W 2 ) strains in vitro. The Peter’s 4-day suppressive tests (4DTs) was used to evaluate the in vivo antimalaria activity using P. berghei ANKA strain, lumefantrine resistant (LuR), and piperaquine resistant (PQR) P. berghei lines. In silico prediction of absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles was assayed using PreADMET online prediction tool. The reference drug in all experiments was artesunate (ATS). Statistical significance between ATSA’s activities in treated and control mice was evaluated by one-way analysis of variance (ANOVA). Results show that inhibitory concentrations-50 (IC 50 ) of ATSA is 11.47 ± 1.3 (3D 7 ) and 1.45 ± 0.26 (W 2 ) against 4.66 ± 0.93 (3D 7 ) and 0.60 ± 0.15 (W 2 ) ng/ml of ATS with a selective index of 2180.91(3D 7 ) and a therapeutic index (TI) of > 71). No mortalities were observed in acute oral toxicity assays and mean weight differences for test and controls were statistically insignificant ( P > 0.05). The in vivo activity of ATSA was above 40% with effective dosage-50 (ED 50 ) of 4.211, 2.601, and 3.875 mg/kg body weight against P. berghei ANKA , LuR, and PQR lines, respectively. The difference between treated and control mice was statistically significant ( P < 0.05). ATSA has high intestinal absorption (HIA) > 95% and has medium human ether-a-go-go related gene (hERG) K + channel inhibition risks. Preclinical and clinical studies on ATSA are recommended to evaluate its value in developing novel drugs for future management of multi-drug resistant malaria parasites.

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Section: Introductionmentioning

confidence: 99%

Antimalarial activity assay of artesunate-3-chloro-4(4-chlorophenoxy) aniline in vitro and in mice models

et al. 2023

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“…This sequestration of infected RBCs (iRBCs) in vital organs such as brain, kidney, lungs etc can make the infection fatal (22)(23)(24)(25). Malariaexposed individuals do show presence of anti-PfEMP1 antibodies which have shown to be neutralizing and protective in nature (26)(27)(28)(29)(30). Overall, the PfEMP1 proteins and the merozoite surface proteins together make ideal candidates that have immunodominancy and can be targeted to reduce the disease burden and severity.…”

Section: Introductionmentioning

confidence: 99%

Multi-protein chimeric antigens, a novel combined approach for efficiently targeting and blocking the blood stage ofPlasmodium falciparum

Deshmukh,

Khatri,

Kochar

et al. 2023

Preprint

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Plasmodium falciparum-induced malaria remains a fatal disease affecting millions of people worldwide. Mainly, the blood stage of malaria is highly pathogenic and symptomatic, rapidly damaging the host organs and occasionally leading to death. Currently, no vaccines are approved for use against the blood stage of malaria. Canonical vaccines in the past have selected the most immunodominant or essential protein to block the growth of the parasite. This strategy works efficiently for low-complexity organisms such as viruses and a few bacteria but has not shown promising results for a malaria vaccine.Plasmodiumhas a complex life cycle and vaccine candidates especially during blood stage are ineffective due to multiple gene families showing redundancy, immune evasion, and insufficient antibody titer. Herein, we demonstrate a novel strategy of combining multiple antigens from the blood stage ofPlasmodium falciparumusing only the most immunodominant peptide sequences as a way of tackling polymorphism and redundancy. We created three chimeric antigens targeting eight PfEMP1 proteins (chimeric varB) and eight merozoite surface proteins (chimeric MSP and InvP) by selecting and stitching B-cell epitopes. Our chimeric constructs show naturally circulating antibodies against individual peptides using epitope-mapping microarray as well as entire proteins in malaria-infected patients. We demonstrate that anti-varB antibodies are neutralizing in nature and significantly reduce the cytoadhesion on an organ-on-chip system with a microfluidic device mimicking physiological conditions. We have applied a Deep Learning based method to quantify the number of adhered RBCs under fluidic conditions that is used to study cytoadhesion. Furthermore, the anti-MSP and InvP antibodies show complete growth inhibition in a single cycle at a combined concentration of 0.13 mg/ml. Overall, our results show that a combination of antigenic peptides from multiple antigens can function as a next-generation vaccine and effectively block the blood stage by reducing cytoadhesion and inhibiting the parasite growth.

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“…This protein is known to have an affinity with ICAM-1 receptor and estimated to have conserved epitopes, so it is considered as a candidate for a peptide-based malaria vaccine (9) . Identificatifying of T-cell and B-cell epitopes is crucial in designing the malaria vaccine because the protective immunity against malaria depends on the ability of both cells in generating immune responses (10) . Determination of the T-cell and B-cell epitopes of the recombinant protein will be useful for further study in developing a peptide-based vaccine.…”

Section: Introductionmentioning

confidence: 99%

Epitopes prediction of PfEMP1-DBL2? recombinant protein from Indonesian Plasmodium falciparum Isolate for malaria vaccine development

2020

MLU

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The development of an effective vaccine against malaria is essential. Domain Duffy-binding-like (DBL)2β in Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) protein is one of the vaccine candidate proteins because of its binding capacity to ICAM-1 receptor. However, the high polymorphism needs epitope identification before formulating a peptide-based vaccine. This study aimed to identify the conserved epitopes in PfEMP1-DBL2β by an immunoinformatic approach. The protein sequences were analyzed to predict the hydrophobicity attributes, T-cell and B-cell epitopes. T-cell epitopes were identified using the NetCTL and Propred server and analyzed for population coverage rate using the IEDB analysis tool. Moreover, the Bepipred 2.0 and Kolaskar Tangaonkar method combined with the K-means clustering were used to predict the B-cell epitopes. This study found that the hydrophobicity value of PfEMP1-DBL2β recombinant protein is 32.62, indicating that this protein is soluble and potentially fit into HLA alleles active site. Two conserved antigenic CTL epitopes with near 90% population coverage rate in the malaria target population were identified. For Th cell epitopes, the NN-align algorithm showed no overlapping strong binding epitope positions for three chosen Indonesian and African alleles. Three B-cell conserved epitopes were identified at the position of 77-89, 236-254 and 360-377 amino acids with one cluster overlapping with ICAM-1 determinant binding area. The predicted conserved epitopes within the protein in this study are valuable in constructing a subunit peptide-based malaria vaccine candidate. A further experimental study is needed to validate this approach as the next step in vaccine development.

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Acquisition of naturally acquired antibody response to Plasmodium falciparum erythrocyte membrane protein 1-DBLα and differential regulation of IgG subclasses in severe and uncomplicated malaria

Cited by 3 publications

References 33 publications

Antimalarial activity assay of artesunate-3-chloro-4(4-chlorophenoxy) aniline in vitro and in mice models

Antimalarial activity assay of artesunate-3-chloro-4(4-chlorophenoxy) aniline in vitro and in mice models

Multi-protein chimeric antigens, a novel combined approach for efficiently targeting and blocking the blood stage ofPlasmodium falciparum

Epitopes prediction of PfEMP1-DBL2? recombinant protein from Indonesian Plasmodium falciparum Isolate for malaria vaccine development

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