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Babesia Bovis Ligand-Receptor Interaction: AMA-1 Contains Small Regions Governing Bovine Erythrocyte Binding

Cuy-Chaparro, Laura; Bohórquez, Michel David; Arevalo-Pinzon, Gabriela; Castañeda-Ramírez, Jeimmy Johana; Suárez, Carlos F. (2021)

Apical membrane antigen 1 is a microneme protein which plays an indispensable role during Apicomplexa parasite invasion. The detailed mechanism of AMA-1 molecular interaction with its receptor on bovine erythrocytes has ...
Critical role of HLA-DRβ* binding peptides' peripheral flanking residues in fully-protective malaria vaccine development

Reyes, Cesar; Rojas Luna, Rocío; Aza Conde, Jorge; Tabares, Luisa; Patarroyo, Manuel A.; Patarroyo, Manuel Elkin (2017)

A vaccine candidate component must fit perfectly into the antigen presenting HLA-DRβ* molecule's groove (or canonical nonapeptide) peptide binding region (PBR) during antigen presentation to the T-cell receptor (TCR), ...
Malaria: Paving the way to developing peptide-based vaccines against invasion in infectious diseases

Reyes, César; Molina Franky, Jessica S.; Aza Conde, Jorge; Suárez, Carlos F.; Pabón, Laura; Moreno Vranich, Armando; Patarroyo, Manuel A.; Patarroyo, Manuel Elkin (2020)

Malaria remains a large-scale public health problem, killing more than 400,000 people and infecting up to 230 million worldwide, every year. Unfortunately, despite numerous efforts and research concerning vaccine development, ...

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Babesia Bovis Ligand-Receptor Interaction: AMA-1 Contains Small Regions Governing Bovine Erythrocyte Binding
...
Cuy-Chaparro, Laura | 2021

Apical membrane antigen 1 is a microneme protein which plays an indispensable role during Apicomplexa parasite invasion. The detailed mechanism of AMA-1 molecular interaction with its receptor on bovine erythrocytes has not been completely defined in Babesia bovis. This study was focused on identifying the minimum B. bovis AMA-1-derived regions governing specific and high-affinity binding to its target cells. Different approaches were used for detecting ama-1 locus genetic variability and natural selection signatures. The binding properties of twelve highly conserved 20-residue-long peptides were evaluated using a sensitive and specific binding assay based on radio-iodination. B. bovis AMA-1 ectodomain structure was modelled and refined using molecular modelling software. NetMHCIIpan software was used for calculating B-and T-cell epitopes. The B. bovis ama-1 gene had regions under functional constraint, having the highest negative selective pressure intensity in the Domain I encoding region. Interestingly, B. bovis AMA-1-DI (100YMQKFDIPRNHGSGIYVDLG119 and120GYESVGSKSYRMPVGKCPVV139 ) and DII (302CPMHPVRDAIFGKWSGGSCV321 )-derived peptides had high specificity interaction with erythrocytes and bound to a chymotrypsin and neuraminidase-treatment sensitive receptor. DI-derived peptides appear to be exposed on the protein’s surface and contain predicted B-and T-cell epitopes. These findings provide data (for the first-time) concerning B. bovis AMA-1 functional subunits which are important for establishing receptor-ligand interactions which could be used in synthetic vaccine development.

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Critical role of HLA-DRβ* binding peptides' peripheral flanking residues in fully-protective malaria vaccine development
...
Reyes, Cesar | 2017

A vaccine candidate component must fit perfectly into the antigen presenting HLA-DRβ* molecule's groove (or canonical nonapeptide) peptide binding region (PBR) during antigen presentation to the T-cell receptor (TCR), conforming a specific and stable macromolecular complex and induce an appropriate immune response. Antigen's peripheral flanking residues (PFR, positions (p) -p2 and p10) must thus establish strong interactions with the HLA-DRβ* - TCR complex. These amino acids (aa) have specific physico-chemical characteristics enabling differentiation between non-protective but antibody-inducer (NPAI), short-lived protection inducer (SLPI) and long-lasting protection inducer (LLPI) peptides when used as an antimalarial vaccine component. Their identification (through 1H-NMR and Aotus monkey immunization) and proper modification contributes to a logical and rational methodology for long-lasting and protective immunological memory.

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Malaria: Paving the way to developing peptide-based vaccines against invasion in infectious diseases
...
Reyes, César | 2020

Malaria remains a large-scale public health problem, killing more than 400,000 people and infecting up to 230 million worldwide, every year. Unfortunately, despite numerous efforts and research concerning vaccine development, results to date have been low and/or strain-specific. This work describes a strategy involving Plasmodium falciparum Duffy binding-like (DBL) and reticulocyte-binding protein homologue (RH) family-derived minimum functional peptides, netMHCIIpan3.2 parental and modified peptides’ in silico binding prediction and modeling some Aotus major histocompatibility class II (MHCII) molecules based on known human molecules’ structure to understand their differences. These are used to explain peptides’ immunological behaviour when used as vaccine components in the Aotus model. Despite the great similarity between human and Aotus immune system molecules, around 50% of Aotus allele molecules lack a counterpart in the human immune system which could lead to an Aotus-specific vaccine. It was also confirmed that functional Plasmodium falciparum’ conserved proteins are immunologically silent (in both the animal model and in-silico prediction); they must therefore be modified to elicit an appropriate immune response. Some peptides studied here had the desired behaviour and can thus be considered components of a fully-protective antimalarial vaccine.

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Browsing by Subject "Merozoítos"

Babesia Bovis Ligand-Receptor Interaction: AMA-1 Contains Small Regions Governing Bovine Erythrocyte Binding ﻿

Critical role of HLA-DRβ* binding peptides' peripheral flanking residues in fully-protective malaria vaccine development ﻿

Malaria: Paving the way to developing peptide-based vaccines against invasion in infectious diseases ﻿

Envíos recientes

Babesia Bovis Ligand-Receptor Interaction: AMA-1 Contains Small Regions Governing Bovine Erythrocyte Binding

Critical role of HLA-DRβ* binding peptides' peripheral flanking residues in fully-protective malaria vaccine development

Malaria: Paving the way to developing peptide-based vaccines against invasion in infectious diseases

Babesia Bovis Ligand-Receptor Interaction: AMA-1 Contains Small Regions Governing Bovine Erythrocyte Binding

Critical role of HLA-DRβ* binding peptides' peripheral flanking residues in fully-protective malaria vaccine development

Malaria: Paving the way to developing peptide-based vaccines against invasion in infectious diseases