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BackgroundCD4+ T-cell epitopes play a crucial role in eliciting vigorous protective immune responses during peptide (epitope)-based vaccination. The prediction of these epitopes focuses on the peptide binding process by MHC class II proteins. The ability to account for MHC class II polymorphism is critical for epitope-based vaccine design tools, as different allelic variants can have different peptide repertoires. In addition, the specificity of CD4+ T-cells is often directed to a very limited set of immunodominant peptides in pathogen proteins. The ability to predict what epitopes are most likely to dominate an immune response remains a challenge.ResultsWe developed the computational tool Predivac to predict CD4+ T-cell epitopes. Predivac can make predictions for 95% of all MHC class II protein variants (allotypes), a substantial advance over other available methods. Predivac bases its prediction on the concept of specificity-determining residues. The performance of the method was assessed both for high-affinity HLA class II peptide binding and CD4+ T-cell epitope prediction. In terms of epitope prediction, Predivac outperformed three available pan-specific approaches (delivering the highest specificity). A central finding was the high accuracy delivered by the method in the identification of immunodominant and promiscuous CD4+ T-cell epitopes, which play an essential role in epitope-based vaccine design.ConclusionsThe comprehensive HLA class II allele coverage along with the high specificity in identifying immunodominant CD4+ T-cell epitopes makes Predivac a valuable tool to aid epitope-based vaccine design in the context of a genetically heterogeneous human population.The tool is available at: http://predivac.biosci.uq.edu.au/.

Novel vaccination approaches based on rational design of B-and T-cell epitopes -epitope-based vaccinesare making progress in the clinical trial pipeline. The epitope-focused recombinant protein-based malaria vaccine (termed RTS,S) is a next-generation approach that successfully reached phase-III trials, and will potentially become the first commercial vaccine against a human parasitic disease. Progress made on methods such as recombinant DNA technology, advanced cell-culture techniques, immunoinformatics and rational design of immunogens are driving the development of these novel concepts. Synthetic recombinant proteins comprising both B-and T-cell epitopes can be efficiently produced through modern biotechnology and bioprocessing methods, and can enable the induction of large repertoires of immune specificities. In particular, the inclusion of appropriate CD4+ T-cell epitopes is increasingly considered a key vaccine component to elicit robust immune responses, as suggested by results coming from HIV-1 clinical trials. In silico strategies for vaccine design are under active development to address genetic variation in pathogens and several broadly protective "universal" influenza and HIV-1 vaccines are currently at different stages of clinical trials. Other methods focus on improving population coverage in target populations by rationally considering specificity and prevalence of the HLA proteins, though a proof-of-concept in humans has not been demonstrated yet. Overall, we expect immunoinformatics and bioprocessing methods to become a central part of the next-generation epitope-based vaccine development and production process.

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Gold nanoparticles (AuNPs) are currently under intense investigation for biomedical and biotechnology applications, thanks to their ease in preparation, stability, biocompatibility, multiple surface functionalities, and size-dependent optical properties. The most commonly used method for AuNP synthesis in aqueous solution is the reduction of tetrachloroauric acid (HAuCl4) with trisodium citrate. We have observed variations in the pH and in the concentration of the gold colloidal suspension synthesized under standard conditions, verifying a reduction in the reaction yield by around 46% from pH 5.3 (2.4 nM) to pH 4.7 (1.29 nM). Citrate-capped AuNPs were characterized by UV-visible spectroscopy, TEM, EDS, and zeta-potential measurements, revealing a linear correlation between pH and the concentration of the generated AuNPs. This result can be attributed to the adverse effect of protons both on citrate oxidation and on citrate adsorption onto the gold surface, which is required to form the stabilization layer. Overall, this study provides insight into the effect of the pH over the synthesis performance of the method, which would be of particular interest from the point of view of large-scale manufacturing processes.

Emissions of hydrogen sulfide (H

Removal of Pb(ii), Cu(ii) and Cd(ii) was attained using hydroxyapatite nanocrystals derived from clam shells, in batch and column experiments.