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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, ...
Structural analysis of owl monkey MHC-DR shows that fully-protective malaria vaccine components can be readily used in humans

Suárez, Carlos F.; Pabón, Laura; Barrera, Ana; Aza Conde, Jorge; Patarroyo, Manuel Alfonso; Patarroyo, Manuel Elkin (2017)

More than 50 years ago the owl monkey (genusAotus) was found to be highly susceptible to developinghuman malaria, making it an excellent experimental model for this disease. Microbes and parasites'(especially malaria) ...

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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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Structural analysis of owl monkey MHC-DR shows that fully-protective malaria vaccine components can be readily used in humans
...
Suárez, Carlos F. | 2017

More than 50 years ago the owl monkey (genusAotus) was found to be highly susceptible to developinghuman malaria, making it an excellent experimental model for this disease. Microbes and parasites'(especially malaria) tremendous genetic variability became resolved during our malaria vaccine devel-opment, involving conserved peptides having high host cell binding activity (cHABPs); however, cHABPsare immunologically silent and must be specially modified (mHABPs) to induce a perfectfit into majorhistocompatibility complex (MHC) molecules (HLA in humans). Since malarial immunity is mainlyantibody-mediated and controlled by the HLA-DRB genetic region, ~1000Aotushave been molecularlycharacterised for MHC-DRB, revealing striking similarity between human andAotusMHC-DRB reper-tories. Such convergence suggested that a large group of immune protection-inducing protein structures(IMPIPS), highly immunogenic and protection inducers against malarial intravenous challenge inAotus,could easily be used in humans for inducing full protection against malaria. We highlight the value of alogical and rational methodology for developing a vaccine in an appropriate animal model:Aotusmonkeys

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Browsing by Author "Aza Conde, Jorge"

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 ﻿

Structural analysis of owl monkey MHC-DR shows that fully-protective malaria vaccine components can be readily used in humans ﻿

Envíos recientes

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

Structural analysis of owl monkey MHC-DR shows that fully-protective malaria vaccine components can be readily used in humans

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

Structural analysis of owl monkey MHC-DR shows that fully-protective malaria vaccine components can be readily used in humans