Acquired immune responses to three malaria vaccine candidates and their relationship to invasion inhibition in two populations naturally exposed to malaria

Background: Malaria still represents a major cause of morbidity and mortality predominantly in several developing countries, and remains a priority in many public health programmes. Despite the enormous gains made in control and prevention the development of an effective vaccine represents a persisting challenge. Although several para site antigens including pre-erythrocytic antigens and blood stage antigens have been thoroughly investigated, the identification of solid immune correlates of protection against infection by Plasmodium falciparum or clinical malaria remains a major hurdle. In this study, an immuno-epidemiological survey was carried out between two populations naturally exposed to P. falciparum malaria to determine the immune correlates of protection. Methods: Plasma samples of immune adults from two countries (Ghana and Madagascar) were tested for their reactivity against the merozoite surface proteins MSP1-19, MSP3 and AMA1 by ELISA. The antigens had been selected on the basis of cumulative evidence of their role in anti-malarial immunity. Additionally, reactivity against crude P. falciparum lysate was investigated. Purified IgG from these samples were furthermore tested in an invasion inhibition assay for their antiparasitic activity. Results: Significant intra- and inter- population variation of the reactivity of the samples to the tested antigens were found, as well as a significant positive correlation between MSP1-19 reactivity and invasion inhibition (p < 0.05). Interestingly, male donors showed a significantly higher antibody response to all tested antigens than their female counterparts. In vitro invasion inhibition assays comparing the purified antibodies from the donors from Ghana and Madagascar did not show any statistically significant difference. Although in vitro invasion inhibition increased with breadth of antibody response, the increase was not statistically significant. Conclusions: The findings support the fact that the development of semi-immunity to malaria is probably con tingent on the development of antibodies to not only one, but a range of antigens and that invasion inhibition in immune adults may be a function of antibodies to various antigens. This supports strategies of vaccination including multicomponent vaccines as well as passive vaccination strategies with antibody cocktails

Effect of ph on the synthesis and properties of luminescent sio2/calcium phosphate:eu3+ core-shell nanoparticles

A novel method for the synthesis of luminescent SiO(2)/calcium phosphate (CaP):Eu(3+) core-shell nanoparticles (NPs) was developed via a sol-gel route followed by annealing at a temperature of 800 degrees C. The object of this study was the investigation of the effect of pH on the formation of a CaP shell around the silica core. The resulting annealed NPs exhibited an amorphous SiO(2) core and a crystalline luminescent shell. The formation of a CaP layer was possible at pH below 4.5 and above 6.5 during the coating step. The crystal structure of the shell was studied by X-ray diffraction analysis. Hydroxyapatite (HAp) and alpha-tricalcium phosphate were detected as crystal phases of the surrounding layer. However, NPs produced under basic conditions exhibited a higher crystallinity of the CaP layer than did samples coated at pH below 4.5. In the pH interval between 4.5 and 6.5, no shell growth but the formation of secondary NPs containing CaO and Ca(OH)(2) was observed. Furthermore, SiO(2)/CP:Eu(3+) core-shell NPs were investigated by transmission electron microscopy, dynamic light scattering, Fourier transform infrared spectroscopy, inductively coupled plasma optical emission spectrometry, and photoluminescence spectroscopy. The resulting HAp-coated NPs were successfully tested by a cell-culture-based viability assay with respect to a later application as a luminescent marker for biomedical applications

Anti-plasmodium parasite antibodies

The technology provided herein relates to novel human antibodies against Plasmodium parasites, in particular against the malaria parasite Plasmodium falciparum. The present disclosure pertains to antibodies against apical membrane antigen 1 (AMA-1). These antibodies have high affinity e.g. to Plasmodium falciparum schizonts and merozoites, inhibit the reinvasion of merozoites into erythrocytes and thereby neutralize parasitic multiplication

Molecular Targeting Therapy against EGFR Family in Breast Cancer. Progress and Future Potentials

The epidermal growth factor receptor (EGFR) family contains four transmembrane tyrosine kinases (EGFR1/ErbB1, Her2/ErbB2, Her3/ErbB3 and Her4/ErbB4) and 13 secreted polypeptide ligands. EGFRs are overexpressed in many solid tumors, including breast, pancreas, head-and-neck, prostate, ovarian, renal, colon, and non-small-cell lung cancer. Such overexpression produces strong stimulation of downstream signaling pathways, which induce cell growth, cell differentiation, cell cycle progression, angiogenesis, cell motility and blocking of apoptosis. The high expression and/or functional activation of EGFRs correlates with the pathogenesis and progression of several cancers, which make them attractive targets for both diagnosis and therapy. Several approaches have been developed to target these receptors and/or the EGFR modulated effects in cancer cells. Most approaches include the development of anti-EGFRs antibodies and/or small-molecule EGFR inhibitors. This review presents the state-of-the-art and future prospects of targeting EGFRs to treat breast cancer

Production and characterisation of monoclonal antibodies against RAI3 and its expression in human breast cancer

Abstract Background RAI3 is an orphan G-protein coupled receptor (GPCR) that has been associated with malignancy and may play a role in the proliferation of breast cancer cells. Although its exact function in normal and malignant cells remains unclear and evidence supporting its role in oncogenesis is controversial, its abundant expression on the surface of cancer cells would make it an interesting target for the development of antibody-based therapeutics. To investigate the link with cancer and provide more evidence for its role, we carried out a systematic analysis of RAI3 expression in a large set of human breast cancer specimens. Methods We expressed recombinant human RAI3 in bacteria and reconstituted the purified protein in liposomes to raise monoclonal antibodies using classical hybridoma techniques. The specific binding activity of the antibodies was confirmed by enzyme-linked immunosorbent assay (ELISA), western blot and immunocytochemistry. We carried out a systematic immunohistochemical analysis of RAI3 expression in human invasive breast carcinomas (n = 147) and normal breast tissues (n = 44) using a tissue microarray. In addition, a cDNA dot blot hybridisation assay was used to investigate a set of matched normal and cancerous breast tissue specimens (n = 50) as well as lymph node metastases (n = 3) for RAI3 mRNA expression. Results The anti-RAI3 monoclonal antibodies bound to recombinant human RAI3 protein with high specificity and affinity, as shown by ELISA, western blot and ICC. The cDNA dot blot and immunohistochemical experiments showed that both RAI3 mRNA and RAI3 protein were abundantly expressed in human breast carcinoma. However, there was no association between RAI3 protein expression and prognosis based on overall and recurrence-free survival. Conclusion We have generated a novel, highly-specific monoclonal antibody that detects RAI3 in formaldehyde-fixed paraffin-embedded tissue. This is the first study to report a systematic analysis of RAI3 expression in normal and cancerous human breast tissue at both the mRNA and protein levels.</p