Induction and displacement of an α helix in the 6725 SERA peptide analogue confers protection against P. falciparum malaria

Based on HLA-DRβ1* Allele Binding Specificities, Striking Differences in Distance and TCR Contacting Residue Orientation can be Observed in Modified Protection-Inducing Malarial Synthetic Peptides

“…However, whereas some HABPs modifications elicited non-protection inducing antibodies in vaccinated Aotus monkeys, [(some induced antibodies having a very short half-life) [119]], other modifications made to HABPs were able to induce high antibody titres against parasite native protein and protected Aotus monkeys from challenge with the highly infective P. falciparum FVO strain [101][102][103][104][105][106][107][108][109][110][111][112][113][114][115][116]. Although the protection levels achieved by each of these modified HABPs has been limited (Table 1), and individually slightly lower than SPf66, the purpose of our Institute it is to develop a rational methodology for obtaining multi-antigenic, multi-stage, subunit-based synthetic vaccines, malaria being one of them.…”

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

“…1 H-NMR (600 mHz) was used for determining and analysing more than 300 20-mer long cHABP (non-immunogenic) and mHABP (protection-inducing) 3D structures [67,68,74,78]. Recognising their binding motifs and binding registers in their amino acid sequences, together with data from molecular docking and Aotus immunisation studies led to the observation that the 3D structure of functionally relevant, native HABPs involved in the invasion of target cells were almost identical to those they displayed in recombinant protein structure determined by x-ray crystallography (regardless of the methodology used for determining them) [79].…”

“…Much of the recent body of our work has dealt with the immunogenicity (IFA and WB assays) of individual Mrz-and Spz-derived mHABPs and their protection-inducing ability by the most stringent test available (intravenous inoculation of a highly virulent Aotus-adapted P. falciparum strain), showing that mHABPs from Mrz and Spz parasite stages cover most MHC II genetic variants and face the parasite regarding two lines of defence: Spz and Mrz invasion [11,67,68,74,76,78,84,89,90].…”

Protective immunity provided by a new modified SERA protein peptide: its immunogenetic characteristics and correlation with 3D structure

“…In previous studies (Puentes et al 2000), 49 non-overlapping 20 residue-long peptides encompassing the whole SERA protein were synthesised; six native peptides showed high binding capacity to RBCs, named high-activity binding peptides (HABPs): 6725 (Alba et al 2004), 6733 (this paper), 6737 (Cubillos et al 2003), 6746 , 6754 (this paper) and 6762 (Salazar et al 2008). They were numbered according to our institute's peptide coding system, meaning that their localisation (Fig.…”

“…Our previous studies have also identified modified peptides derived from other SERA-conserved HABPs [6725 (Alba et al 2004), 6737 (Cubillos et al 2003), 6746 and 6762 (Salazar et al 2008)] which were able to induce high immune responses and protective immunity, highlighting them as strong vaccine candidates. The present manuscript has concentrated on studying native peptides 6733 and 6754 (which displayed random configuration 3D structures as determined by CD and 1 H-NMR studies) known to be involved in RBC invasion due to the aforementioned studies.…”