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It has been found that conserved peptide 1818 belonging to plasmodium falciparum protein has high red blood cell binding capacity that plays an important role in invasion process. The results show that modifications made to critical binding residues induce strong structural changes in nonstructured, nonimunogenic, nonprotection inducing peptides making them fit into specific class-II molecules such as HLA-DRbeta(sub 1)*1101.

The life cycle of Plasmodium falciparum and the intimate molecular interactions of the molecules involved in the parasite's invasion of red blood cells (RBCs) are discussed. The vaccination with a molecule having genetic variability has suppressed the immune response and hence recognizing conserved high-activity binding peptides (HABPs) is required, which is done by chemically synthesizing small fragments or HABPs leading to the recognition of such function.

Abstract: EBA-175 protein is used as ligand in Plasmodium falciparum binding to erythrocytes. Evidence shows that conserved peptide 1815 from this protein having high red blood cell binding ability plays an important role in the invasion process. This peptide is neither immunogenic nor protective. Residues were substituted by amino acids having similar volume or mass but different polarity in 1815 analogues had to make them fit into HLA-DRβ1*03 molecules; these were synthesised and inoculated into Aotus monkeys, generating different immunogenic and/or protective immune responses. A shortening in α-helix structure was found in the immunogenic and protective ones when their secondary structure was analyzed by NMR to correlate their structure with their immunological properties. This data, together with results from previous studies, suggests that this shortening in high-activity binding peptide (HABP) helical configuration may lead to better fitting into immune system molecules as shown by binding to purified HLA-DRβ1* molecules rendering them immunogenic and protective and therefore, excellent candidates for consideration as components of a subunit based multi-component synthetic vaccine against malaria. [Copyright &y& Elsevier]

The erythrocyte binding antigen EBA- 175 is a 175-kDa Plasmodium falciparum protein, which has been shown to be involved in the process of invasion of erythrocytes. It has been found that conserved peptide 1818 belonging to this protein has high red blood cell binding capacity and plays an important role in the invasion process. This peptide is neither immunogenic nor protective. Peptide 1818 analogues had some of their previously recognized critical red blood cell binding residues substituted for amino acids having similar volume or mass but different polarity to make them fit into HLA-DRβ1*1101 molecules; these 1818 peptide analogues were then synthesized and inoculated into Aotus nancymaae monkeys, generating different immunogenic and/or protective immune responses. Short structures such as 310-helix, classical, or distorted type-III β-turns were found in the immunogenic and protective peptides once the secondary structure had been analyzed by NIMR and its structure correlated with its immunological properties. These data suggest that peptide flexibility may lead to better fitting into immune system molecules, therefore making them excellent candidates for consideration as components of a subunit-based, multicomponent synthetic antimalarial vaccine. [ABSTRACT FROM AUTHOR]

A 175-erythrocyte-binding protein (EBA-175) conserved high-activity binding peptide (HABP), called 1783 (nonimmunogenic, nonprotective against Plasmodium falciparum malaria), was analyzed for antigenic and protective activity in Aotus monkeys, together with several of its analogues. 1H NMR studies of peptides 17912, 14016, and 22814 allowed their structure to be related to their biological function. These peptides showed helical regions having differences in their position and length. Nonimmunogenic, nonprotective peptides 1783 and 17912 showed an extensive helical region, while the 22814 immunogenic protective peptide’s α-helix was found in the N-terminal region. This suggests that the more flexible C-terminal region will allow better interaction between these peptides and immune system molecules as well as relating these peptides’ three-dimensional structure to their immunogenicity and protective activity, thus leading to a more rational development of the new malaria multicomponent vaccine. [Copyright &y& Elsevier]

EBA-175 protein is used as a ligand in the binding of P. falciparum to red blood cells (RBCs). Evidence shows that the conserved peptide 1779 from this protein (with high red blood cell binding ability and known critical erythrocyte binding residues) plays an important role in the invasion process. This peptide is neither immunogenic nor protective; analogs having critical residues replaced by amino acids with similar volume or mass but different polarity were synthesized and inoculated into Aotus monkeys, and elicited different immunogenic and protective responses. Nuclear Magnetic Resonance (1H-NMR) studies revealed that peptide analog 21696 (non-immunogenic and non-protective) presents a large helical fragment, that the peptide 14012 (immunogenic and non-protective) helical fragment is smaller, while the peptide 22812 (immunogenic and protective) alpha-helix is shorter in a different region and possesses greater flexibility at its N-terminus. The presence of methionine residues could affect the structural stability of peptide 22812 and ultimately its immunological response. Our results suggest a new strategy for designing a new malaria multi-component subunit-based vaccine.