Estudio conformacional de péptidos modificados de las proteínas STARP, CelTOS, TRSP y SERA 5 de Plasmodium falciparum y su relación con una respuesta inmune en malaria

Abstract

Developing an anti-malarial vaccine represents a dynamic area for exploration, even though one having enormous challenges, especially due to the complexity of the parasite’s lifecycle. Plasmodium falciparum’s different invasion stages must thus be blocked and the greatest amount of information possible concerning the artillery to be used in its attack must be extracted from them. Peptides from (sporozoite-derived) STARP, CelTOS and TRSP and (merozoite-derived) SERA 5 proteins having high binding affinity for HepG2 cells and red blood cells, respectively (known as conserved HABPs), have thus been modified, synthesised and evaluated at immune response level in Aotus monkeys as well as having been studied regarding their structural conformation by 1H-NMR.

The results have shown that native peptides are not immunogenic, but can induce high antibody titres when their critical or neighbouring residues are replaced by others having similar volume and mass but different polarity. Conformational study has revealed that native peptide structures are different from that of their modified peptides, having shorter or longer structured regions or not having any compared to their highly immunogenic modified analogues. Particular stereo-chemical characteristics in the side-chains of some of these modified peptides’ amino acid residues, such as physical-chemical features, seem to play an important role in inducing an appropriate immune response when they have been immunised in groups of Aotus monkeys, thereby complementing the design of a totally effective vaccine against malaria.