Erratum to “Peptides of the liver stage antigen-1 (LSA-1) of Plasmodium falciparum bind to human hepatocytes”

a de Colombia, Universidad Nacional de Colombia, Bogotá, Colombia.
Peptides (Impact Factor: 2.62). 06/2003; 24(5):647-57. DOI: 10.1016/S0196-9781(03)00135-9
Source: PubMed


Synthetic peptides from the liver stage antigen-1 (LSA-1) antigen sequence were used in HepG2 cell and erythrocyte binding assays to identify regions that could be involved in parasite invasion. LSA-1 protein peptides 20630 ((21)INGKIIKNSEKDEIIKSNLRY(40)), 20637 ((157)KEKLQGQQSDSEQERRAY(173)), 20638 ((174)KEKLQEQQSDLEQERLAY(190)) and 20639 (191KEKLQEQQSDLEQERRAY(207)) had high binding activity in HepG2 assays. Were located in immunogenic regions; peptide cell binding was saturable. Peptide 20630 bound specifically to 48kDa HepG2 membrane surface protein. LSA-1 peptides 20630 ((21)INGKIIKNSEKDEIIKSNLRY(40)) and 20633 ((81)DKELTMSNVKNVSQTNFKSLY(100)) showed specific erythrocyte binding activity and inhibited merozoite invasion of erythrocytes in vitro. A monkey serum prepared against LSA-1 20630 peptide analog (CGINGKNIKNAEKPMIIKSNLRGC) inhibited merozoite invasion in vitro. The data suggest LSA-1 "High Activity Binding Peptides" could play a possible role in hepatic cell invasion as well as merozoite invasion of erythrocytes.

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    • "(D) Same analysis performed with sera collected from monkeys immunized with modified peptides 24,276 and 24,402 recognizing the recombinant SALSA protein (47 and 42.4 kDa). correlates with a proliferative response to 3 T-cell epitopes, the specially variable T1 epitope (residues 84–107) which contains our variable HABP 20,633 [6], T3 (residues 1813–1835) and T5 (1818–1909) [21] [22]. None of these T-cell epitopes included conserved HABPs, which poses a tremendous problem for the development of an antimalarial vaccine with global coverage, due to the parasite's tremendous genetic variability. "
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    ABSTRACT: A fully effective antimalarial vaccine must contain multiple proteins from the different development stages of Plasmodium falciparum parasites involved in host-cell invasion or their biologically active fragments. It must therefore include sporozoite molecules able to induce protective immunity by blocking the parasite's access to hepatic cells, and/or proteins involved in the development of this stage, amongst which are included the Liver Stage Antigen-1 (LSA-1) and the Sporozoite and Liver Stage Antigen (SALSA). Our studies have focused on the search for an association between the structure of high activity binding peptides (HABPs), including both conserved native and their modified analogues, and their ability to bind to the MHC Class II HLA-DR molecules during formation of the MHCII-peptide-TCR complex leading to inducing the appropriate immune response. These studies are part of a logical and rational strategy for developing multi-stage, multi-component, minimal subunit-based vaccines, mainly against the P. falciparum malaria.
    Biochemical and Biophysical Research Communications 06/2009; 384(4):455-60. DOI:10.1016/j.bbrc.2009.04.138 · 2.30 Impact Factor
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    • "These RBCs were poured into polystyrene tubes with increasing 125 I-peptide concentrations (0 and 40 nM) in the presence or absence of unlabelled peptide (40 excess) at 10% hematocrite and 200 ␮l final volume; they were then incubated for 90 min at room temperature with constant shaking. Then cells were washed three times with 3 ml HBS and cell-associated radioactivity was quantified on an Automatic Gamma Counter (4/200 plus, ICN) [6] [8] [9] [17] [20] [24]. Binding assays were also done with HABP jumbled-peptide analogue sequences (peptides having the same amino-acid composition as HABPs but having random sequence) to determine whether HABP binding to red blood cells was due to their specific amino-acid sequence or just the amino-acid composition. "
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    ABSTRACT: Synthetic 20-mer long non-overlapped peptides, from STEVOR protein, were tested in RBC binding assays for identifying STEVOR protein regions having high RBC binding activity and evaluating whether these regions inhibit Plasmodium falciparum in vitro invasion. Affinity constants, binding site number per cell and Hill coefficients were determined by saturation assay with high activity binding peptides (HABPs). HABP binding assays using RBCs previously treated with enzymes were carried out to study the nature of the receptor. The molecular weight of RBC surface proteins interacting with HABPs was determined by cross-linking assays and SDS-PAGE analysis. RBC binding assays revealed that peptides 30561 (41MKSRRLAEIQLPKCPHYNND60), 30562 (61PELKKIIDKLNEERIKKYIE80) and 30567 (161ASCCKVHDNYLDNLKKGCFG180) bound saturably and with high binding activity, presenting nanomolar affinity constants. HABP binding activity to RBCs previously treated with neuraminidase and trypsin decreased, suggesting that these peptides bound to RBC surface proteins and that such binding could be sialic acid dependent. Cross-linking and SDS-PAGE assays showed that the three HABPs specifically bound to 30 and 40 kDa molecular weight RBC membrane proteins. Peptides 30561, 30562 and 30567 inhibited P. falciparum in vitro invasion of red blood cells in a concentration-dependent way. Goat sera having STEVOR protein polymeric peptides antibodies inhibit parasite in vitro invasion depending on concentration. Three peptides localized in STEVOR N-terminal and central regions had high, saturable, binding activity to 30 and 40 kDa RBC membrane proteins. These peptides inhibited the parasite's in vitro invasion, suggesting that STEVOR protein regions are involved in P. falciparum invasion processes during intra-erythrocyte stage.
    Peptides 08/2005; 26(7):1133-43. DOI:10.1016/j.peptides.2005.01.013 · 2.62 Impact Factor
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    ABSTRACT: This work determined Plasmodium falciparum merozoite surface protein-8 (MSP-8) regions specifically binding to membrane surface receptors on human erythrocytes. Five high activity binding peptides (HABPs), whose binding to erythrocytes became saturable and sensitive on being treated with neuraminidase and chymotrypsin were identified from the MSP-8 protein. Those amino acids directly involved in interaction with erythrocytes were also determined for each one of the HABPs. Some of them specifically recognized 28, 46, and 73 kDa erythrocyte membrane proteins. Some HABPs inhibited in vitro P. falciparum merozoite invasion of erythrocytes by up to 98%, suggesting the MSP-8 protein's possible role in the invasion process.
    Peptides 08/2003; 24(7):1015-23. DOI:10.1016/S0196-9781(03)00185-2 · 2.62 Impact Factor
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