Rotavirus spike protein ΔVP8* as a novel carrier protein for conjugate vaccine platform with demonstrated antigenic potential for use as bivalent vaccine

Conjugate vaccine platform is a promising strategy to overcome the poor immunogenicity of bacterial polysaccharide antigens in infants and children. A carrier protein in conjugate vaccines works not only as an immune stimulator to polysaccharide, but also as an immunogen; with the latter generally not considered as a measured outcome in real world. Here, we probed the potential of a conjugate vaccine platform to induce enhanced immunogenicity of a truncated rotavirus spike protein ΔVP8*. ΔVP8* was covalently conjugated to Vi capsular polysaccharide (Vi) of Salmonella Typhi to develop a bivalent vaccine, termed Vi-ΔVP8*. Our results demonstrated that the Vi-ΔVP8* vaccine can induce specific immune responses against both antigens in immunized mice. The conjugate vaccine elicits high antibody titers and functional antibodies against S. Typhi and Rotavirus (RV) when compared to immunization with a single antigen. Together, these results indicate that Vi-ΔVP8* is a potent and immunogenic vaccine candidate, thus strengthening the potential of conjugate vaccine platform with enhanced immune responses to carrier protein, including ΔVP8*.

The Contribution of Polysaccharide Antigens From Clinical Proteus spp. and Klebsiella spp. Isolates to the Serological Cross-Reactions

Klebsiella spp. and Proteus spp. cause hospital-acquired urinary tract infections (UTIs), which are often related to the use of catheters. To create a vaccine preventing UTI, immunogenic bacterial antigens with common epitopes are still being looked for. In this work, the role of polysaccharide antigens of four Klebsiella spp. and eight Proteus spp. strains in serological cross-reactions with specific antisera was examined. Enzyme-linked immunosorbent assay (ELISA), Western blotting, and silver staining by Tsai method were performed. The Klebsiella and Proteus spp. LPSs and cells were used as antigens. Polyclonal rabbit sera specific to Klebsiella oxytoca 0.023 and 0.062 strains and four Klebsiella spp. LPSs were obtained. The ELISA and Western blotting results showed the strongest cross-reactions occurring between lipopolysaccharides (LPSs) from four Klebsiella strains and P. vulgaris O42 antiserum. The silver-staining procedure revealed the patterns typical of both slow- and fast-migrating mass species of the Klebsiella LPSs. The Klebsiella spp. antigens also cross-reacted with four P. penneri antisera, and most of the reactions were observed as low-migrating patterns. From two K. oxytoca antisera obtained in this work, only one, the K. oxytoca 0.062 antiserum, cross-reacted with satisfactory strength with P. penneri LPSs (19, 22, and 60). Obtaining cross-reactions between the antigens of Klebsiella strains and Proteus antisera and in the opposite systems is important for proving the immunogenic role of polysaccharide antigens in triggering the immunological response.

Computational and NMR Conformational Analysis of Galactofuranoside Cycles Presented in Bacterial and Fungal Polysaccharide Antigens

Unlike pyranoside cycles which are generally characterized by strictly defined conformational preferences, furanosides are flexible and may adopt a wide range of available conformations. During our previous studies, conformational changes of galactofuranoside cycles upon total sulfation were described computationally, using a simple Hartree–Fock (HF) method, and principal conformers of the 5-membered galactose ring were revealed. However, in the case of more complex disaccharide structures, it was found that this method and the widely applied DFT-B3LYP produced results that deviated from experimental evidence. In this study, other DFT functionals (PBE0 and double hybrid B2PLYP) along with RI-MP2 are employed to study the conformational behavior of the galactofuranoside ring. Reinvestigation of galactofuranosides with a lactic acid substituent at O-3 revealed that changes in the orientation of lactic acid residue at O-3 might induce conformational changes of the furanoside cycle. Such findings are important for further modeling of carbohydrate–protein interaction.

THE ROLE OF PROTEINS OF STREPTOCOCCUS PNEUMONIAE IN THE DEVELOPMENT OF SEROTYPE-INDEPENDENT PNEUMOCOCCAL VACCINES

Infections caused by Streptococcus pneumoniae are relevant for Russia and the world. One of the key factors in the pathogenicity of pneumococcus is a polysaccharide capsule. The structure of polysaccharide antigens is described more than 90 serotypes of the pathogen. The experience of using polysaccharide and conjugated pneumococcal vaccines shows that these preventive drugs protect against a limited number of serotypes of the pneumococcus. It is of interest to study the protective properties of pneumococcal proteins, as they are conservative and have high homology within the species, potentially expanding serotype non-specific protection level. Thus, the efforts of researchers focus on the development of protein vaccines or conjugated vaccines based on proteins of S. pneumoniae. The review considers the biological properties of the most well-known proteins of pneumococcus and provides data on preclinical studies of the obtained recombinant proteins as experimental vaccine preparations. Immunization with various proteins of S. pneumoniae provides protection of animals from nasopharyngeal colonization, pneumonia and sepsis. Currently, clinical trials (I/II phases) are being tested with several experimental protein vaccines. In the near future it will be possible to assess the real effectiveness of such vaccines.

Probiotics in Autoimmune and Inflammatory Disorders

Probiotics have been used to ameliorate gastrointestinal symptoms since ancient times. Over the past 40 years, probiotics have been shown to impact the immune system, both in vivo and in vitro. This interaction is linked to gut microbes, their polysaccharide antigens, and key metabolites produced by these bacteria. At least four metabolic pathways have been implicated in mechanistic studies of probiotics, based on mechanistic studies in animal models. Microbial–immune system crosstalk has been linked to: short-chain fatty acid production and signaling, tryptophan metabolism and the activation of aryl hydrocarbon receptors, nucleoside signaling in the gut, and activation of the intestinal histamine-2 receptor. Several randomized controlled trials have now shown that microbial modification by probiotics may improve gastrointestinal symptoms and multiorgan inflammation in rheumatoid arthritis, ulcerative colitis, and multiple sclerosis. Future work will need to carefully assess safety issues, selection of optimal strains and combinations, and attempts to prolong the duration of colonization of beneficial microbes.

Probiotics in Autoimmune and Inflammatory Disorders

Probiotics have been used to ameliorate gastrointestinal symptoms since ancient times. Over the past 40 years, probiotics have been shown to exert major effects on the immune system, both in vivo and in vitro.  This interaction is clearly linked to gut microbes, their polysaccharide antigens, and key metabolites produced by these bacteria.  At least four metabolic pathways have been implicated in mechanistic studies of probiotics, based on carefully studied animal models.  Microbial-immune system crosstalk has been linked to short chain fatty acid production and signaling, tryptophan metabolism and the activation of aryl hydrocarbon receptors, nucleoside signaling in the gut, and activation of the intestinal histamine-2 receptor.  Several randomized controlled trials have now shown that microbial modification by probiotics may improve gastrointestinal symptoms and multi-organ inflammation in rheumatoid arthritis, ulcerative colitis, and multiple sclerosis.  Future work will need to carefully assess safety issues, selection of optimal strains and combinations, and attempts to prolong the duration of colonization of beneficial microbes.