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Adjuvants approved for human use: What do we know and what do we need to know for designing good adjuvants?

Reyes, César; Patarroyo, Manuel-Alfonso (2023)

Adjuvants represent one of the most significant biotechnological solutions regarding vaccine development, thereby broadening the amount of candidates which can now be used and tested in vaccine formulations targeting various ...
Conserved binding regions provide the clue for peptide-based vaccine development: A chemical perspective

Curtidor, Hernando; Reyes, César; Bermúdez, Adriana; Vanegas, Magnolia; Varela, Yahson; Patarrollo, Manuel Elkin (2017)

Abstract: Synthetic peptides have become invaluable biomedical research and medicinal chemistry tools for studying functional roles, i.e., binding or proteolytic activity, naturally-occurring regions’ immunogenicity in ...
Critical role of HLA-DRb* binding peptides' peripheralflankingresidues in fully-protective malaria vaccine development

Reyes, César; 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, ...
Plasmodium falciparum pre-erythrocytic stage vaccine development

Molina Franky, Jessica; Cuy Chaparro, Laura; Camargo, Anny; Reyes, César; Gómez, Marcela; Salamanca, David Ricardo; Patarroyo, Manuel Alfonso; Patarroyo, Manuel Elkin (2020)

Worldwide strategies between 2010 and 2017 aimed at controlling malarial parasites (mainly Plasmodium falciparum) led to a reduction of just 18% regarding disease incidence rates. Many biologically-derived anti-malarial ...
SM-COLSARSPROT: Highly Immunogenic Supramutational Synthetic Peptides Covering the World’s Population

Patarroyo, Manuel-Alfonso; Patarroyo, Manuel-Elkin; Pabón, Laura; Alba, Martha patricia; Bermudez, Adriana; Rugeles, María Teresa; Diaz-Arevalo, Diana; Zapata, Wildeman; Zapata, María Isabel; Reyes, César; Suarez, Carlos F.; Agudelo, William (2022)

Fifty ~20–amino acid (aa)–long peptides were selected from functionally relevant SARS-CoV-2 S, M, and E proteins for trial B-21 and another 53 common ones, plus some new ones derived from the virus’ main genetic variants ...
The role of pi-interactions and hydrogen bonds in fully protective synthetic malaria vaccine development

Reyes, César; Moreno-Vranich, Armando; Patarroyo, Manuel Elkin (2017)

Analysis of ourPlasmodium falciparummalaria parasite peptides'1H-NMR database in the search for H-bonds andp-interactions led us to correlate their presence or absence with a peptide's particularimmunological behavior. It ...

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Adjuvants approved for human use: What do we know and what do we need to know for designing good adjuvants?
...
Reyes, César | 2023

Adjuvants represent one of the most significant biotechnological solutions regarding vaccine development, thereby broadening the amount of candidates which can now be used and tested in vaccine formulations targeting various pathogens, as antigens which were previously discarded due to their low or null immunogenicity can now be included. Adjuvant development research has grown side-by-side with an increasing body of knowledge regarding immune systems and their recognition of foreign microorganisms. Alum-derived adjuvants were used in human vaccines for many years, even though complete understanding of their vaccination-related mechanism of action was lacking. The amount of adjuvants approved for human use has increased recently in line with attempts to interact with and stimulate the immune system. This review is aimed at summarising what is known about adjuvants, focusing on those approved for use in humans, their mechanism of action and why they are so necessary for vaccine candidate formulations; it also discusses what the future may hold in this growing research field

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Conserved binding regions provide the clue for peptide-based vaccine development: A chemical perspective
...
Curtidor, Hernando | 2017

Abstract: Synthetic peptides have become invaluable biomedical research and medicinal chemistry tools for studying functional roles, i.e., binding or proteolytic activity, naturally-occurring regions’ immunogenicity in proteins and developing therapeutic agents and vaccines. Synthetic peptides can mimic protein sites; their structure and function can be easily modulated by specific amino acid replacement. They have major advantages, i.e., they are cheap, easily-produced and chemically stable, lack infectious and secondary adverse reactions and can induce immune responses via T- and B-cell epitopes. Our group has previously shown that using synthetic peptides and adopting a functional approach has led to identifying Plasmodium falciparum conserved regions binding to host cells. Conserved high activity binding peptides’ (cHABPs) physicochemical, structural and immunological characteristics have been taken into account for properly modifying and converting them into highly immunogenic, protection-inducing peptides (mHABPs) in the experimental Aotus monkey model. This article describes stereo–electron and topochemical characteristics regarding major histocompatibility complex (MHC)-mHABP-T-cell receptor (TCR) complex formation. Some mHABPs in this complex inducing long-lasting, protective immunity have been named immune protection-inducing protein structures (IMPIPS), forming the subunit components in chemically synthesized vaccines. This manuscript summarizes this particular field and adds our recent findings concerning intramolecular interactions (H-bonds or π-interactions) enabling proper IMPIPS structure as well as the peripheral flanking residues (PFR) to stabilize the MHCII-IMPIPS-TCR interaction, aimed at inducing long-lasting, protective immunological memory

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Critical role of HLA-DRb* binding peptides' peripheralflankingresidues in fully-protective malaria vaccine development
...
Reyes, César | 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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Plasmodium falciparum pre-erythrocytic stage vaccine development
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Molina Franky, Jessica | 2020

Worldwide strategies between 2010 and 2017 aimed at controlling malarial parasites (mainly Plasmodium falciparum) led to a reduction of just 18% regarding disease incidence rates. Many biologically-derived anti-malarial vaccine candidates have been developed to date; this has involved using many experimental animals, an immense amount of work and the investment of millions of dollars. This review provides an overview of the current state and the main results of clinical trials for sporozoite-targeting vaccines (i.e. the parasite stage infecting the liver) carried out by research groups in areas having variable malaria transmission rates. However, none has led to promising results regarding the effective control of the disease, thereby making it necessary to complement such efforts at finding/introducing new vaccine candidates by adopting a multi-epitope, multi-stage approach, based on minimal subunits of the main sporozoite proteins involved in the invasion of the liver.

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SM-COLSARSPROT: Highly Immunogenic Supramutational Synthetic Peptides Covering the World’s Population
...
Patarroyo, Manuel-Alfonso | 2022

Fifty ~20–amino acid (aa)–long peptides were selected from functionally relevant SARS-CoV-2 S, M, and E proteins for trial B-21 and another 53 common ones, plus some new ones derived from the virus’ main genetic variants for complementary trial C-21. Peptide selection was based on tremendous SARS-CoV-2 genetic variability for analysing them concerning vast human immunogenetic polymorphism for developing the first supramutational, Colombian SARS-protection (SM-COLSARSPROT), peptide mixture. Specific physicochemical rules were followed, i.e., aa predilection for polyproline type II left-handed (PPIIL) formation, replacing β-branched, aromatic aa, short-chain backbone H-bond-forming residues, π-π interactions (n→π* and π-CH), aa interaction with π systems, and molecular fragments able to interact with them, disrupting PPIIL propensity formation. All these modified structures had PPIIL formation propensity to enable target peptide interaction with human leukocyte antigen-DRβ1* (HLA-DRβ1*) molecules to mediate antigen presentation and induce an appropriate immune response. Such modified peptides were designed for human use; however, they induced high antibody titres against S, M, and E parental mutant peptides and neutralising antibodies when suitably modified and chemically synthesised for immunising 61 major histocompatibility complex class II (MHCII) DNA genotyped Aotus monkeys (matched with their corresponding HLA-DRβ1* molecules), predicted to cover 77.5% to 83.1% of the world’s population. Such chemically synthesised peptide mixture represents an extremely pure, stable, reliable, and cheap vaccine for COVID-19 pandemic control, providing a new approach for a logical, rational, and soundly established methodology for other vaccine development.

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The role of pi-interactions and hydrogen bonds in fully protective synthetic malaria vaccine development
...
Reyes, César | 2017

Analysis of ourPlasmodium falciparummalaria parasite peptides'1H-NMR database in the search for H-bonds andp-interactions led us to correlate their presence or absence with a peptide's particularimmunological behavior. It was concluded that a 26.5±1.5 Å between positions 1 to 9 of the HLA-DRb1*interacting region was necessary for proper docking of 20mer-long peptides and these MHC Class IImolecules for full-protective immunity. Presence of intramolecular H-bonds orp-interactions leading torigh-handeda-helix orb-turn conformation in this peptide's region induces different immune responsesor none. PPIILconformation and the absence of any intramolecular interaction thus became thefirstfeature characterising our immune protection-inducing structures as malaria vaccine candidates

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Browsing by Author "Reyes, César"

Adjuvants approved for human use: What do we know and what do we need to know for designing good adjuvants? ﻿

Conserved binding regions provide the clue for peptide-based vaccine development: A chemical perspective ﻿

Critical role of HLA-DRb* binding peptides' peripheralflankingresidues in fully-protective malaria vaccine development ﻿

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

Plasmodium falciparum pre-erythrocytic stage vaccine development ﻿

SM-COLSARSPROT: Highly Immunogenic Supramutational Synthetic Peptides Covering the World’s Population ﻿

The role of pi-interactions and hydrogen bonds in fully protective synthetic malaria vaccine development ﻿

Envíos recientes

Adjuvants approved for human use: What do we know and what do we need to know for designing good adjuvants?

Conserved binding regions provide the clue for peptide-based vaccine development: A chemical perspective

Critical role of HLA-DRb* binding peptides' peripheralflankingresidues in fully-protective malaria vaccine development

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

Plasmodium falciparum pre-erythrocytic stage vaccine development

SM-COLSARSPROT: Highly Immunogenic Supramutational Synthetic Peptides Covering the World’s Population

The role of pi-interactions and hydrogen bonds in fully protective synthetic malaria vaccine development

Adjuvants approved for human use: What do we know and what do we need to know for designing good adjuvants?

Conserved binding regions provide the clue for peptide-based vaccine development: A chemical perspective

Critical role of HLA-DRb* binding peptides' peripheralflankingresidues in fully-protective malaria vaccine development

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

Plasmodium falciparum pre-erythrocytic stage vaccine development

SM-COLSARSPROT: Highly Immunogenic Supramutational Synthetic Peptides Covering the World’s Population

The role of pi-interactions and hydrogen bonds in fully protective synthetic malaria vaccine development