In silico integrative analysis predicts relevant properties of exotoxin-derived peptides for the design of vaccines against Pseudomonas aeruginosa.

Pseudomonas aeruginosa (PA) is an opportunistic human pathogen responsible for causing serious infections in patients with cystic fibrosis. Infections caused by PA are difficult to treat and eradicate due to intrinsic and added resistance to antibiotic therapy. Therefore, it is necessary to establish effective prevention strategies against this infectious agent. In this study, a combination of immunoinformatic tools was applied to predict immunogenic and immunodominant regions in the structure of exotoxins commonly secreted as virulence factors in PA infection (ExoA, ExoS, ExoT, ExoU and ExoY). The peptides derived from exotoxins were evaluated for the potential affinity for human leukocyte antigen (HLA) I and HLA-II molecules, antigenicity score and toxicity profile. From an initial screening of 941 peptides, 13 (1.38%) were successful in all analyzes. The peptides with relevant immunogenic properties were mainly those derived from Exo A (10 / 76.9%). All peptides selected in the last analysis present a high population coverage rate based on the interaction of HLA alleles (95.36 ± 7.83%). Therefore, the peptides characterized in this study are recommended for in vitro and in vivo studies and can provide the basis for the rational design of a vaccine against PA.

Bovine serum albumin nanoparticles induce histopathological changes and inflammatory cell recruitment in the skin of treated mice.

Albumin is a natural, biocompatible, biodegradable and nontoxic polymer and due to these features, nanoparticles made of albumin are a good system for drug or antigen delivery. Polymeric nanoparticles are being widely explored as new vaccines platforms due to the capacity of those nanoparticles to prime the immune system by providing sustained release of the antigen after injection. Biodegradable nanoparticles associated with proteins represent a promising method for in vivo delivery of vaccines. In our previous studies, bovine serum albumin nanoparticles (BSA-NPs) were identified as a promising system for in vivo delivery of microbial antigens. The aim of this work was to show the effect of BSA-NPs on skin after nanoparticles administration. The pro-inflammatory activity of BSA-NPs was evaluated using in vivo models. BSA-NPs are easily uptake by macrophagic RAW 264.7 and BHK-21 cells without any significant cytotoxicity. Histological examination of skin sections from BSA-NPs-treated mice revealed intense cellular infiltration, increased skin thickness, follicular hypertrophy, vascular congestion and marked collagenesis. Mice immunized with recombinant non-structural protein 1 (rNS1) from Dengue virus 1 and BSA-NPs showed a high seroconversion rate if compared to animals immunized only with rNS1. Therefore, the effect of BSA-NPs on skin after BSA-NPs administration has a biotechnological relevance to the rational design of vaccine formulations based on albumin nanocarriers. However in the next years future studies should be carried out to best characterize the effect of BSA-NPs on dendritic cells and establish the role of these nanoparticles as a new vaccine platform for infectious diseases or cancer.