Recent advances in the development of a chemically synthesised anti-malarial vaccine

Curtidor, Hernando; Patarroyo, Manuel Elkín

doi:10.1517/14712598.2015.1075505

Cited by 12 publications

(6 citation statements)

References 105 publications

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“…A significant amount of HABPs have been identified in most P. falciparum proteins participating in Spz and Mz invasion of their respective target cells (Rodriguez et al, ; Curtidor, Vanegas, Alba, & Patarroyo, ). After HABPs have undergone a series of chemical modifications and structural and immunological studies, they have been able to induce a strong protection‐inducing immune response in experimental challenge in a non‐human primate animal model (Curtidor, Patarroyo, & Patarroyo, ). Such HABPs have now been defined as immune protection‐inducing protein structures (IMPIPS), and some of them are strong candidates for a multiantigen, multistage, subunit‐based anti‐ P. falciparum vaccine (Patarroyo et al, ).…”

Section: Resultsmentioning

confidence: 99%

Receptor-ligand and parasite protein-protein interactions inPlasmodium vivax: Analysing rhoptry neck proteins 2 and 4

Bermúdez

Arévalo-Pinzón

Rubio

et al. 2018

Cellular Microbiology

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Elucidating receptor-ligand and protein-protein interactions represents an attractive alternative for designing effective Plasmodium vivax control methods. This article describes the ability of P. vivax rhoptry neck proteins 2 and 4 (RON2 and RON4) to bind to human reticulocytes. Biochemical and cellular studies have shown that two PvRON2- and PvRON4-derived conserved regions specifically interact with protein receptors on reticulocytes marked by the CD71 surface transferrin receptor. Mapping each protein fragment's binding region led to defining the specific participation of two 20 amino acid-long regions selectively competing for PvRON2 and PvRON4 binding to reticulocytes. Binary interactions between PvRON2 (ligand) and other parasite proteins, such as PvRON4, PvRON5, and apical membrane antigen 1 (AMA1), were evaluated and characterised by surface plasmon resonance. The results revealed that both PvRON2 cysteine-rich regions strongly interact with PvAMA1 Domains II and III (equilibrium constants in the nanomolar range) and at a lower extent with the complete PvAMA1 ectodomain and Domains I and II. These results strongly support that these proteins participate in P. vivax's complex invasion process, thus providing new pertinent targets for blocking P. vivax merozoites' specific entry to their target cells.

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Section: Resultsmentioning

confidence: 99%

Receptor-ligand and parasite protein-protein interactions inPlasmodium vivax: Analysing rhoptry neck proteins 2 and 4

Bermúdez

Arévalo-Pinzón

Rubio

et al. 2018

Cellular Microbiology

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“…The specific binding plot was obtained from the difference between total binding (binding in the absence of non-radiolabeled peptide) and unspecific binding (binding in the presence of non-radiolabeled peptide) plots 74 . Peptides having ≥0.02 slope specific binding plot were considered high activity binding peptides (HABPs) and used as templates for designing an anti-malarial vaccine 75 . Some HABPs were conserved (no amino acid sequence variation) and others had genetic variability and elicited a strain-specific immune response allowing malarial parasites to escape vaccine-induced immunity, meaning that they were discarded from further immunological studies 74 .…”

Section: Resultsmentioning

confidence: 99%

Plasmodium vivax ligand-receptor interaction: PvAMA-1 domain I contains the minimal regions for specific interaction with CD71+ reticulocytes

Arévalo-Pinzón

Bermúdez

Hernández

et al. 2017

Sci Rep

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The malarial parasite’s invasion is complex, active and coordinated, involving many low and high affinity interactions with receptors on target cell membrane. Proteomics analysis has described around 40 proteins in P. vivax which could be involved in reticulocyte invasion; few have been studied with the aim of elucidating how many of them establish specific interactions with their respective host cells. Given the importance of knowing which of the parasite’s protein regions are functionally important for invasion, minimum regions mediating specific interaction between Plasmodium vivax apical membrane antigen 1 (PvAMA-1) and its host cell were here elucidated. The region covering PvAMA-1 domains I and II (PvAMA-DI-II) specifically bound to the CD71+ red blood cell subpopulation. A 20 residue-long region (81EVENAKYRIPAGRCPVFGKG100) located in domain I was capable of inhibiting PvAMA-DI-II recombinant protein binding to young reticulocytes (CD71+CD45−) and rosette formation. This conserved peptide specifically interacted with high affinity with reticulocytes (CD71+) through a neuraminidase- and chymotrypsin-treatment sensitive receptor. Such results showed that, despite AMA-1 having universal functions during late Plasmodium invasion stages, PvAMA-1 had reticulocyte-preferring binding regions, suggesting that P. vivax target cell selection is not just restricted to initial interactions but maintained throughout the erythrocyte invasion cycle, having important implications for designing a specific anti-P. vivax vaccine.

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“…Smp_311670) putatively able to stimulate mouse and human MHC class II, and a linear B-cell peptide of 20 amino acids (SmKB) based on physicochemical properties able to produce a humoral response. These in silico analyses are considered feasible, fast, and accurate in designing subunit vaccines against infectious diseases and could produce chemically and structurally defined safer vaccines that are easier to manufacture and store than conventional ones (68). We formulated these two candidates in the ADAD vaccination system developed by our group to overcome the issues of the experimental Freund's adjuvant (54, 55).…”

Section: Discussionmentioning

confidence: 99%

Peptides Derived of Kunitz-Type Serine Protease Inhibitor as Potential Vaccine Against Experimental Schistosomiasis

et al. 2019

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Schistosomiasis is a significant public health problem in sub-Saharan Africa, China, Southeast Asia, and regions of South and Central America affecting about 189 million people. Kunitz-type serine protease inhibitors have been identified as important players in the interaction of other flatworm parasites with their mammalian hosts. They are involved in host blood coagulation, fibrinolysis, inflammation, and ion channel blocking, all of them critical biological processes, which make them interesting targets to develop a vaccine. Here, we evaluate the protective efficacy of chemically synthesized T- and B-cell peptide epitopes derived from a kunitz protein from Schistosoma mansoni. Putative kunitz-type protease inhibitor proteins were identified in the S. mansoni genome, and their expression was analyzed by RNA-seq. Gene expression analyses showed that the kunitz protein Smp_147730 (Syn. Smp_311670) was dramatically and significantly up-regulated in schistosomula and adult worms when compared to the invading cercariae. T- and B-cell epitopes were predicted using bioinformatics tools, chemically synthesized, and formulated in the Adjuvant Adaptation (ADAD) vaccination system. BALB/c mice were vaccinated and challenged with S. mansoni cercariae. Kunitz peptides were highly protective in vaccinated BALB/c mice showing significant reductions in recovery of adult females (89–91%) and in the numbers of eggs trapped in the livers (77–81%) and guts (57–77%) of mice. Moreover, liver lesions were significantly reduced in vaccinated mice (64–65%) compared to infected control mice. The vaccination regime was well-tolerated with both peptides. We propose the use of these peptides, alone or in combination, as reliable candidates for vaccination against schistosomiasis.

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Recent advances in the development of a chemically synthesised anti-malarial vaccine

Cited by 12 publications

References 105 publications

Receptor-ligand and parasite protein-protein interactions inPlasmodium vivax: Analysing rhoptry neck proteins 2 and 4

Receptor-ligand and parasite protein-protein interactions inPlasmodium vivax: Analysing rhoptry neck proteins 2 and 4

Plasmodium vivax ligand-receptor interaction: PvAMA-1 domain I contains the minimal regions for specific interaction with CD71+ reticulocytes

Peptides Derived of Kunitz-Type Serine Protease Inhibitor as Potential Vaccine Against Experimental Schistosomiasis

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