Protection against malaria is conferred by passive transferring rabbit F(ab)(2)' antibody fragments, induced by Plasmodium falciparum MSP-1 site-directed designed pseudopeptide-BSA conjugates assessed in a rodent model |
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| Authors: | Lozano José Manuel Lesmes Liliana Patricia Gallego Gina Marcela Patarroyo Manuel Elkin |
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| Affiliation: | a Fundación Instituto de Inmunología de Colombia (FIDIC) and Universidad del Rosario, Bogotá, DC, Colombia
b Universidad Nacional de Colombia, Bogotá, DC, Colombia |
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| Abstract: | F(ab)2′-immunoglobulin (Ig) fragments induced by site-directed designed immunogens are emerging as novel tools of potential utility in the treatment of clinical episodes of transmissible diseases such as malaria. Immunogens based on reduced amide pseudopeptides based on site-directed molecular modifications represent structural probes that could be considered as novel vaccine candidates, as we have previously demonstrated.We have obtained F(ab)2′-Ig rabbit antibodies induced against the N-terminal sequence of the native Merozoite Surface Protein-1 (MSP-1) of Plasmodium falciparum and a set of five MSP-1-derived reduced amide pseudopeptides. Pseudopeptides were designed for inducing functional neutralizing mono-specific polyclonal antibodies with potential applications in the control of malaria. Following a classical enzyme immunoglobulin fractionation, F(ab)2′-Ig fragments were tested for their ability to suppress blood-stage parasitemia by passive immunization in malaria-infected mice. Some of these fragments proved totally effective in suppressing a lethal blood-stage challenge infection and others reduced malarial parasitemia.These data suggest that protection against Plasmodium yoelii malaria following passive transfer of structurally well-defined β-strand F(ab)2′-Ig fragments can be associated with specific immunoglobulins induced by site-directed designed MSP-1 reduced amide pseudopeptides. |
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| Keywords: | F(ab)&prime 2, antibody fragment for antigen binding HABP, high activity binding peptide ψ-[CH2NH], reduced amide isoster bond MHC, major histocompatibility complex TCR, T-cell receptor TCC, T-cell clone APC, antigen presenting cell CDR, complimentarily determinant region HLA, human leukocyte antigens IL-4, interleulin-4 INF-γ, gamma interferon mAb, monoclonal antibody MSA-1 or MSP-1, Merozoite Surface Antigen-1 MSA-2 or MSP-2, Merozoite Surface Antigen-2 RBCs, red blood cells iRBC, infected red blood cell CSP, circumsporozoite surface protein IgM, immunoglobulin-M isotype IgG, immunoglobulin-G isotype F(ab)2&prime , immunoglobulins antigen binding fragment-2 NaBH(OAc)3, triacetoxyborohydride DMF, N,N&prime -dimethylformamide DCE, dichloroethane THF, tetrahydrofuran NaCNBH3, sodium cyanoborohydride Pd/C, palladium over charcoal 4-MBHA, 4-methylbenzhydrilamine t-Boc, tert-butyloxycarbonyl Fmoc, 9-fluorenylmethyloxycarbonyl DIEA, diisopropylethylamine TFA, trifluoroacetic acid TFE, trifluoroethanol m-R,S-TMD, 2,2,5-trimethyl-1,3-dioxane-4,6-dione RP-HPLC, reverse-phase high-performance liquid chromatography [D6]DMSO, deuterated-dimethylsulfoxide 1H-NMR, proton-nuclear magnetic resonance CD, Circular Dichroism NOE, Nuclear Overhauser effect SPf-66, synthetic Plasmodium falciparum-66 vaccine |
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