Immunogenicity of synthetic peptides derived from Plasmodium falciparum proteins

Zerpa, Noraida; Wide, Albina; Noda, José A.; Bermúdez, Henry; Pabón, Rosalba; Noya, Óscar

doi:10.1016/j.exppara.2006.01.007

Cited by 18 publications

(14 citation statements)

References 28 publications

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“…These results suggested that pre-erythrocytic Lsa1-41, Salsa1, Glurp, Lsa1J and Lsa3NR2 peptides appeared to be most antigenic, giving the highest proportion of seropositive, and therefore could be potential serological markers of malaria transmission. However, it can not be excluded that differences in antigenicity levels (ΔMFI values) between these peptides could be due also to the different structure of repetitive epitopes and to their conformation when they are coupled to the beads, as previously indicated [18]. Furthermore, the specific Ab response levels and the seropositivity (Table 1) to these relevant antigens (Lsa1-41, Salsa1, Glurp, Lsa1J and Lsa3NR2) were investigated according to the village and period of malaria transmission.…”

Section: Resultsmentioning

confidence: 99%

Assessment of exposure to Plasmodium falciparum transmission in a low endemicity area by using multiplex fluorescent microsphere-based serological assays

et al. 2011

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BackgroundThe evaluation of malaria transmission intensity is a crucial indicator for estimating the burden of malarial disease. In this respect, entomological and parasitological methods present limitations, especially in low transmission areas. The present study used a sensitive multiplex assay to assess the exposure to Plasmodium falciparum infection in children living in an area of low endemicity. In three Senegalese villages, specific antibody (IgG) responses to 13 pre-erythrocytic P. falciparum peptides derived from Lsa1, Lsa3, Glurp, Salsa, Trap, Starp, Csp and Pf11.1 proteins were simultaneously evaluated before (June), at the peak (September) and after (December) the period of malaria transmission, in children aged from 1 to 8 years.ResultsCompared to other antigens, a high percentage of seropositivity and specific antibody levels were detected with Glurp, Salsa1, Lsa3NR2, and Lsa1J antigens. The seropositivity increased with age for all tested antigens. Specific IgG levels to Glurp, Salsa1, Lsa3NR2, and Lsa1J were significantly higher in P. falciparum infected children compared to non-infected and this increase is significantly correlated with parasite density.ConclusionThe multiplex assay represents a useful technology for a serological assessment of rapid variations in malaria transmission intensity, especially in a context of low parasite rates. The use of such combined serological markers (i.e. Glurp, Lsa1, Lsa3, and Salsa) could offer the opportunity to examine these variations over time, and to evaluate the efficacy of integrated malaria control strategies.

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Section: Resultsmentioning

confidence: 99%

Assessment of exposure to Plasmodium falciparum transmission in a low endemicity area by using multiplex fluorescent microsphere-based serological assays

et al. 2011

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“…Antibodies against PfHRP2, such as mAb C1-13, have been reported to bind to PfHRP3 [23]. However, only two bands (50 kDa and 37 kDa) were recognized by mAb D2, while one band (50 kDa) by mAb F9, suggesting these mAbs may have higher specificity than C1-13 [38,39]. …”

Section: Discussionmentioning

confidence: 99%

Production and characterization of specific monoclonal antibodies binding the Plasmodium falciparum diagnostic biomarker, histidine-rich protein 2

Leow

Jones

Cheng³

et al. 2014

Malar J

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BackgroundEarly and accurate diagnosis of Plasmodium falciparum infection is important for providing appropriate treatment to patients with malaria. However, technical limitations of currently available diagnostic tests limit their use in control programs. One possible explanation for the vulnerability of current antibodies used in RDTs is their propensity to degrade at high ambient temperatures. Isolation of new antibodies with better thermal stability represents an appealing approach to improve the performance of RDTs.MethodsIn this study, phage display technology was deployed to isolate novel binders by screening a human naïve scFv antibody library against recombinant Plasmodium falciparum histidine rich protein 2 (rPfHRP2). The isolated scFv clones were reformatted to whole IgG and the recombinant mAbs were produced in a mammalian CHO cell expression system. To verify the biological activity of these purified recombinant mAbs, range of functional assays were characterized.ResultsTwo unique clones (D2 and F9) were isolated after five rounds of biopanning. The reformatted and expressed antibodies demonstrated high binding specificity to malaria recombinant PfHRP2 and native proteins. When 5 μg/mL of mAbs applied, mAb C1-13 had the highest sensitivity, with an OD value of 1, the detection achieved 5 ng/mL of rPfHRP2, followed by mAbs D2 and F9 at 10 ng/mL and 100 ng/mL of rPfHRP2, respectively. Although the sensitivity of mAbs D2 and F9 was lower than the control, these recombinant human mAbs have shown better stability compared to mouse mAb C1-13 at various temperatures in DSC and blot assays. In view of epitope mapping, the predominant motif of rPfHRP2 recognized by mAb D2 was AHHAADAHHA, whereas mAb F9 was one amino acid shorter, resulting in AHHAADAHH. mAb F9 had the strongest binding affinity to rPfHRP2 protein, with a KD value of 4.27 × 10−11 M, followed by control mAb C1-13 at 1.03 × 10−10 M and mAb D2 at 3.05 × 10−10 M.ConclusionsOverall, the performance of these mAbs showed comparability to currently available PfHRP2-specific mouse mAb C1-13. The stability of these novel binders indicate that they merit further work to evaluate their utility in the development of new generation point of care diagnosis of malaria.

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“…These types of antigen-capture-based assays would be of great value for early diagnosis in areas where transmission is high leading to early diagnosis and treatment. In this regard, this research group have recently identified, synthesized and evaluated a series of peptides from different P. falciparum excretory-secretory proteins: glutamate-rich protein (GLURP); histidine-rich protein 2 (HRP2); histidine-rich protein 3 (HRP3); Falciparum interspersed repeat antigen (FIRA) and serine-rich antigen homologous (SERPH) in order to obtain antibodies suitable to be used in an antigen-capture assay [93]. The peptides were used as antigens for the preparation of polyclonal antibodies in rabbits.…”

Section: A5 Severe Acute Respiratory Syndrome (Sars)mentioning

confidence: 99%

“…In the last years, Noya et al [93] have been working on the development of an immunocapture assay based on the use of polyclonal or monoclonal antibodies raised with synthetic peptides. These types of antigen-capture-based assays would be of great value for early diagnosis in areas where transmission is high leading to early diagnosis and treatment.…”

Section: A5 Severe Acute Respiratory Syndrome (Sars)mentioning

confidence: 99%

Synthetic Peptides for the Immunodiagnosis of Human Diseases

Gómara¹,

Haro

2007

CMC

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Synthetic peptides have been shown to be valuable tools for viral laboratory diagnosis and can provide uniform, chemically well-defined antigens for antibody analysis, reducing inter- and intra-assay variation. The main aim in the development of peptide-based diagnostic tests is to recognise specific antibodies induced by the whole viral proteins but using selected short fragments containing the most potent antigenic determinants. The success of this approach depends on the extent to which synthetic peptides are able to mimic the immunodominant epitopes of antigens. In recent years, synthetic peptides that mimic specific epitopes of infectious agents' proteins have been used in diagnostic systems for various human diseases. The present review summarizes some of the drawbacks of the use of relatively short linear peptides as antigenic substrates and the subsequent chemical strategies developed in order to overcome the low peptide reactivity against specific antibodies. Moreover, it outlines the most significant bibliography published in the last five years which provides validated peptide based tests potentially useful for diagnosis of viral, bacterial, parasitic and autoimmune diseases.

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Immunogenicity of synthetic peptides derived from Plasmodium falciparum proteins

Cited by 18 publications

References 28 publications

Assessment of exposure to Plasmodium falciparum transmission in a low endemicity area by using multiplex fluorescent microsphere-based serological assays

Assessment of exposure to Plasmodium falciparum transmission in a low endemicity area by using multiplex fluorescent microsphere-based serological assays

Production and characterization of specific monoclonal antibodies binding the Plasmodium falciparum diagnostic biomarker, histidine-rich protein 2

Synthetic Peptides for the Immunodiagnosis of Human Diseases

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