Structural and Immunological Principles Leading to Chemically Synthesized, Multiantigenic, Multistage, Minimal Subunit-Based Vaccine Development

TCR-contacting residues orientation and HLA-DRβ* binding preference determine long-lasting protective immunity against malaria

“…For more than three decades we have pursued the idea that fully-protective immunity: zero parasites in the blood or spontaneous rapid and permanent recovery after very low parasitaemia (less than 0.1%) can be induced with chemically-synthesized vaccines, based on the concept that functionality relevant conserved high activity binding peptides (cHABP) have to be recognized in the corresponding [10] protein to properly modify them (mHABP) and render them highly immunogenic and protection-inducing [11]. Such minimal subunit-based mHABPs must fulfil set physicochemical and topochemical rules (previously described) to properly display a perfect fitting into MHCII-pep-TCR complex [12].…”

“…mHABPs were synthesized according to Merrifield's peptide synthesis methodology, as modified by Houghten and thoroughly described [10]; a 600 MHz spectrometer was used for determining the 1 H-NMR 3D structure of a large panel of mHABPs [11].…”

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

“…Similar results were obtained when other modifications were made, such as changing critical residues in other analogous peptides synthesised. On the contrary, immunogenicity and protection were induced in Aotus monkeys inoculated with modified HABP 23426 where changes were made to residues T7C, L14H and T16V (Table 1), categorically confirming that critical binding residues or their neighbours have to be changed for others having similar mass and volume but apposite polarity (Cifuentes et al 2008;Patarroyo et al 2008Patarroyo et al , 2011.…”

“…These have been localised in the 47-and 56-kDa fragments, respectively, and form the focus of this manuscript. These native HABPs have been used in the attempt to induce antibodies against the P. falciparum parasite, as well as protective immunity against experimental challenge with this parasite but giving negative results, as has happened with previous experimental data for all conserved HABPs derived from most merozoite proteins studied so far Patarroyo et al 2011). Critical binding residues and some of their neighbours were thus replaced by others having the same mass, volume and surface, but opposite polarity, as represented by black vertical bars (peptides identified as HABPs are indicated by our Institute's serial numbering system).…”

Production of an epitope-specific antibody using recombinant repetitive oligonucleotides

“…As the problems of safety, stability, efficacy and cost of vaccines have become key issues and as advances in molecular biology and biochemistry have allowed for analyses at the gene level in infectious material, vaccine research has proceeded further with diversity. One of the outcomes of this diversification has been the introduction and the development of subunit vaccines that utilise a specific part of the infectious organism (Foged 2011;Patarroyo et al 2011). Such recombinant vaccines may utilise chemically synthesised protein/peptides or genetic manipulation that allows for expression of antigens in other species.…”