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

Abstract

The serine repeat antigen (SERA) protein is a leading candidate molecule for inclusion as a component in a multi-antigen, multi-stage, minimal subunit-based, chemically synthesised anti-malarial vaccine. Peptides having high red blood cell binding affinity (known as HABPs) have been identified in this protein. The 6733 HABP was located in the C-terminal portion of the 47-kDa fragment while HABP 6754 was located in the C-terminal region of the 56-kDa fragment. These conserved HABPs failed to induce an immune response. Critical red blood cell binding residues and/or their neighbours (assessed by glycine-analogue scanning) were replaced by others having the same mass, volume and surface but different polarity, rendering some of them highly immunogenic when assessed by antibody production against the parasite or its proteins and protection-inducers against experimental challenge with a highly infectious Aotus monkey-adapted Plasmodium falciparum strain. This manuscript presents some modified HABPs as vaccine candidate components for enriching our tailor-made anti-malarial vaccine repertoire, as well as their 3D structure obtained by 1H-NMR displaying a short-structured region, differently from the native ones having random structures.

Plasmodium falciparum Blood Stage Antimalarial Vaccines: An Analysis of Ongoing Clinical Trials and New Perspectives Related to Synthetic Vaccines

“…MSP3-derived cHABP 31202 ( 201 Y 220 I) has been located in the MSP3-LSP vaccine’s conserved 95-aa fragment (Figure 2A). SERA-5-derived cHABPs 6725 ( 141 Y– 160 K) and 6733 ( 321 Y– 340 S) (Patarroyo et al, 2011; Bermúdez et al, 2012) are included in the vaccine candidate BK-SE36 recombinant fragment (Figure 2C). P f AMA1-derived cHABP 4313 ( 134 D– 153 G) located in conserved domain 1 and cHABP 4325 ( 374 M– 393 H) in domain 2 are included in the AMA-1 DiCo vaccine candidate (Figure 2D).…”

“…This methodology has enabled testing and selecting mHABP derived from parasite life cycle stages, which has led to promising results in obtaining a highly immunogenic and protection-inducing antimalarial vaccine (Garcia et al, 2007; Rodriguez et al, 2008; Bermúdez et al, 2012; Curtidor et al, 2017). Chemically synthesized vaccines’ main advantages include their high yield, reproducibility, purity (free of contaminants, such as endotoxins), lack of secondary adverse reactions, being able to synthesize unlimited amounts and stability at room temperature for long periods of time (not requiring cold chain) (Bermúdez et al, 2008; Skwarczynski and Toth, 2016).…”

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

“…(F) The structure of the SERA-5 fragment (PDB code 3CH2) [112] with the location of its cHABPs 6746 and 6754, the latter having random structure [113]. These cHABPs establish H-bonds between themselves and are involved in forming the non-canonical enzymatic triad [113].…”

“…(E) The totally random structure of cHABP 5501 [11], agreeing with 19 kDa MSP-1 fragment structure (PDB 1OB1) [111] which is involved in Mrz invasion of RBC and the only one remaining bound to the parasite after RBC invasion. (F) The structure of the SERA-5 fragment (PDB code 3CH2) [112] with the location of its cHABPs 6746 and 6754, the latter having random structure [113]. These cHABPs establish H-bonds between themselves and are involved in forming the non-canonical enzymatic triad [113].…”

Conservation of red blood cell signalling in Plasmodium merozoite invasion

“…Merozoite surface protein containing Duffy binding-like domains (MSPDBL/MSP3.4) has been proposed to bind RBCs (Sakamoto et al, 2012), highlighting a key role in merozoite attachment. Another major group of peripherallyassociated proteins belong to the serine-rich antigen (SERA) family of proteins that possess papain-like protease catalytic domains which are either serine-based (SERA1, SERA2, SERA3, SERA4, SERA5 and SERA9) or cysteine-based (SERA6, SERA7 and SERA8) (Bermúdez et al, 2012;Hodder et al, 2003;Putrianti et al, 2010).…”