The molecular basis for peptide-based antimalarial vaccine development targeting erythrocyte invasion by P. falciparum.
Biochem Biophys Res Commun
; 534: 86-93, 2021 01 01.
Article
in En
| MEDLINE
| ID: mdl-33316544
ABSTRACT
This work describes a methodology for developing a minimal, subunit-based, multi-epitope, multi-stage, chemically-synthesised, anti-Plasmodium falciparum malaria vaccine. Some modified high activity binding peptides (mHABPs) derived from functionally relevant P. falciparum MSP, RH5 and AMA-1 conserved amino acid regions (cHABPs) for parasite binding to and invasion of red blood cells (RBC) were selected. They were highly immunogenic as assessed by indirect immunofluorescence (IFA) and Western blot (WB) assays and protective immune response-inducers against malarial challenge in the Aotus monkey experimental model. NetMHCIIpan 4.0 was used for predicting peptide-Aotus/human major histocompatibility class II (MHCII) binding affinity in silico due to the similarity between Aotus and human immune system molecules; â¼50% of Aotus MHCII allele molecules have a counterpart in the human immune system, being Aotus-specific, whilst others enabled recognition of their human counterparts. Some peptides' 1H-NMR-assessed structural conformation was determined to explain residue modifications in mHABPs inducing secondary structure changes. These directly influenced immunological behaviour, thereby highlighting the relationship with MHCII antigen presentation. The data obtained in such functional, immunological, structural and predictive approach suggested that some of these peptides could be excellent components of a fully-protective antimalarial vaccine.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Plasmodium falciparum
/
Malaria Vaccines
/
Erythrocytes
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2021
Document type:
Article
Affiliation country:
Colombia