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Self-assembled particulate PsaA as vaccine against Streptococcus pneumoniae infection.

ABSTRACT: Streptococcus pneumoniae is a human pathogen responsible for the majority of childhood pneumonia and media otitis cases worldwide. The diversity of its capsular polysaccharides (CPS) results in more than 91 serotypes of which at least 23 are virulent. Various CPS conjugated to immunogenic carrier proteins are currently licensed and provide protection against the infection caused by the respective serotypes but not against new and emerging virulent serotypes. In this study, we considered the conserved protein antigen PsaA, the pneumococcal surface adhesin A, in order to overcome the limitations of CPS antigens. The PsaA was translationally fused to a polyhydroxybutyrate (PHB) synthase which mediated production of PsaA displayed on PHB inclusions in recombinant Escherichia coli. This suggested that the PsaA fusion to the PHB synthase did not interfere with PHB synthase activity and its ability to mediate formation of nano-sized inclusions composed of a PHB core surrounded by the PHB synthase fused to PsaA. Isolated PHB beads showed a negative surface charge. Transmission electron microscopy analysis suggested that the PsaA fusion to the PHB synthase reduced the size of PHB beads from about 500 nm to 100 nm. The integrity and antigenicity of the fusion protein attached to isolated PHB beads was confirmed by SDS-PAGE, tryptic peptide fingerprinting analysis using MALDI-TOF-MS/MS and immunoblotting using a monoclonal anti-PsaA antibody. Mice immunized with PsaA displaying PHB beads produced high and specific IgG levels dominated by IgG1 isotype. While IgG1 titer were similar between soluble and insoluble PsaA, the IgG2 titers were strongly increased upon vaccination with insoluble PsaA i.e. PsaA displayed on PHB beads. Particulate PsaA-PHB beads elicited IgG antibodies recognizing PsaA in whole cell lysates of seven different serotypes of S. pneumoniae. This study suggested that PHB beads are suitable carriers for PsaA in order to induce a significant and specific Th-2-type immune response.

SUBMITTER: Gonzalez-Miro M

PROVIDER: S-EPMC5390691 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Self-assembled particulate PsaA as vaccine against <i>Streptococcus pneumoniae</i> infection.

González-Miro Majela M Rodríguez-Noda Laura L Fariñas-Medina Mildrey M García-Rivera Dagmar D Vérez-Bencomo Vicente V Rehm Bernd H A BHA

Heliyon 20170411 4

<i>Streptococcus pneumoniae</i> is a human pathogen responsible for the majority of childhood pneumonia and media otitis cases worldwide. The diversity of its capsular polysaccharides (CPS) results in more than 91 serotypes of which at least 23 are virulent. Various CPS conjugated to immunogenic carrier proteins are currently licensed and provide protection against the infection caused by the respective serotypes but not against new and emerging virulent serotypes. In this study, we considered t ...[more]

PMID: 28435909

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Project description:Streptococcus pneumoniae is the main cause of diseases such as meningitis, pneumoniae and sepsis, especially in children and old people. Due to costly antibiotic treatment, and increasing resistance of pneumococcus, developing high-efficient protective vaccine against this pathogen is an urgent need. Although the pneumoniae polysaccharide vaccine (PPV) and pneumonia conjugate vaccines (PCV) are the efficient pneumococcal vaccine in children and adult groups, but the serotype replacement of S. pneumoniae strains causes the reduction in efficacy of such vaccines. For overcoming the aforesaid drawbacks epitope-based vaccines are introduced as the relevant alternative. In our previous research, the epitope vaccine was designed based on immunodominant epitopes from PspA, CbpA antigens as cellular stimulants and PhtD, PiuA as humoral stimulants. Because the low immunogenicity is the main disadvantage of epitope vaccine, in the current study, we applied coiled-coil self-assembled structures for developing our vaccine. Recently, self-assembled peptide nanoparticles (SAPNs) have gained much attention in the field of vaccine development due to their multivalency, self-adjuvanticity, biocompatibility, and size similarity to pathogen. In this regard, the final designed vaccine is comprised of cytotoxic T lymphocytes (CTL) epitopes from PspA and CbpA, helper T lymphocytes (HTL) epitopes from PhtD and PiuA, the pentamer and trimmer oligomeric domains form 5-stranded and 3-stranded coiled-coils as self-assembled scaffold, Diphtheria toxoids (DTD) as a universal T-helper, which fused to each other with appropriate linkers. The four different arrangements based on the order of above-mentioned compartments were constructed, and each of them were modeled, and validated to find the 3D structure. The structural, physicochemical, and immunoinformatics analyses of final vaccine construct represented that our vaccine could stimulate potent immune response against S. pneumoniae; however, the potency of that should be approved via various in vivo and in vitro immunological tests.

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Self-assembled particulate PsaA as vaccine against Streptococcus pneumoniae infection.

Publications

Self-assembled particulate PsaA as vaccine against <i>Streptococcus pneumoniae</i> infection.

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