The present application is generally directed to novel pneumococcal polypeptide antigens and nucleic acids encoding such antigens, and immunogenic compositions comprising such antigens for treating and preventing pneumococcal infection. The present invention further provides method of using the antigens to elicits an immune response (e.g., IL-17A response, a T cell-mediated and/or B-cell-mediated immune responses). The present invention also provides methods of prophylaxis and/or treatment of pneumococcal-mediated diseases, such as sepsis, comprising administering an immunogenic composition including one or more of a combination of pneumococcal antigens or functional fragments thereof as disclosed herein. In some embodiments, one or more pneumococcal antigens can be present in a polysaccharide conjugate. The compositions induce an anti-pneumoccocus immune response when administered to a mammal. The compositions can be used prophylactically to vaccinate an individualand/or therapeutically to induce a thereapeutic immune response to an infected individual.

A method is described for producing a pneumococcal capsular polysaccharide protein conjugate in which one or more activated pneumococcal polysaccharides of particular pneumococcal serotypes and carrier protein are separately lyophilized, the separately lyophilized polysaccharides and carrier protein are separately reconstituted in an organic solvent, and the reconstituted polysaccharide and carrier protein are then combined together by Tee-mixing and conjugated together to produce polysaccharide carrier protein conjugates. A plurality of conjugates, each comprising polysaccharides of a particular serotype, may be used to produce multivalent pneumococcal immunogenic compositions having a combination of conjugates for use in vaccines.

An aluminum nanoparticle adjuvant carrier system with stabilizing surface coatings that can efficiently deliver protein or nucleic acid antigen payloads to naive, resident APCs is disclosed.

The present disclosure relates generally to methods of preparing glycoconjugates containing a saccharide conjugated to a carrier protein by use of stable nitroxyl radical related agent/oxidant as an oxidizing agent, to immunogenic compositions comprising such glycoconjugates, and to methods for the use of such glycoconjugates and immunogenic compositions.

A method for determining a disease state prediction, relating to a potential disease or medical condition of a subject, includes accessing a set of subject images, the subject images capturing a part of a subject's body, and accessing a set of clinical factors from the subject. The clinical factors are collected by a device or a medical practitioner substantially contemporaneously with the capture of the subject images. The subject images are inputted into an image model to generate disease metrics for disease prediction for the subject. The disease metrics generated by the image model and the clinical factors are inputted into a classifier to determine the disease state prediction, and the disease state prediction is returned.

The present invention relates to Polysaccharide Size-Reduction Monitoring Methods useful for the non-invasive, and accurate monitoring of the progress of a polysaccharide size-reduction process.

The disclosure provides synthetic (e.g. recombinant) pneumococcal saccharides comprising one or more repeat unit(s) .fwdarw.4)-β-D-Glcp-(1.fwdarw.4)-[Gro-(2.fwdarw.P.fwdarw.3)]-β-D-Galp-(1.fwdarw.4)-β-L-Rhap-(1.fwdarw.. Also provided are conjugates comprising a .fwdarw.4)-β-D-Glcp-(1.fwdarw.4)-[Gro-(2.fwdarw.P.fwdarw.3)]-β-D-Galp-(1.fwdarw.4)-β-L-Rhap-(1.fwdarw., immunogenic compositions, vaccines and their use in preventing or treating infection by Streptococcus pneumoniae.

The disclosure provides synthetic (e.g. recombinant) pneumococcal saccharide comprising one or more repeat unit(s) .fwdarw.4)-β-D-Glcp-(1.fwdarw.3)-[[α-L-Rhap-(1.fwdarw.2)]-[Gro-(2.fwdarw.P.fwdarw.3)]-β-D-Galp-(1.fwdarw.4)]-β-L-Rhap-(1.fwdarw.. Also provided are conjugates comprising a .fwdarw.4)-β-D-Glcp-(1.fwdarw.3)-[[α-L-Rhap-(1.fwdarw.2)]-[Gro-(2.fwdarw.P.fwdarw.3)]-β-D-Galp-(1.fwdarw.4)]-β-L-Rhap-(1.fwdarw., immunogenic compositions, vaccines and their use in preventing or treating infection by Streptococcus pneumoniae.

The disclosure describes compositions containing PEGylated compounds using linkers, bivalent polysaccharide covalent PEG compounds, and methods of bivalent polysaccharide-PEG compounds in the development of multivalent vaccines. PEGylated conjugation of capsular polysaccharides to carrier proteins is carried out using homo-bifunctional and/or hetero-bifunctional linkers of specific lengths. Incorporation of bifunctional PEG linkers induces higher titers of functional antibodies with high avidity, eliciting higher immunologic memory, and reduced carrier protein effect. This provides immunochemically cross-reactive capsular polysaccharides wherein one or more cross-reactive capsular polysaccharides are covalently PEG compounded sequentially or concurrently to carrier protein using bifunctional linkers bearing the same or different functional groups. Such a linker and the size of the capsular polysaccharides provides an effective multivalent vaccine with high antibody titers and a reduced carrier effect, with a reduction in the content of the capsular polysaccharide and protein per dose of vaccine which reduces reactogenicity.

The present invention relates to a carrier protein with site-directed mutation and use thereof in preparation of a vaccine, wherein the carrier protein is selected from fusion proteins formed by one, two or more of diphtheria toxoid, a non-toxic mutant of diphtheria toxin, a bacterial outer membrane protein and a bacterially expressed protein, wherein an amino acid at at least one site on the carrier protein is mutated into an unnatural amino acid, and the unnatural amino acid contains an azido or alkynyl terminal group. In a mutual reaction process of the carrier protein with site-directed mutation of the present invention and a polysaccharide antigen, a covalent bond is formed, and meanwhile a formed conjugate is in a bead-string state, so that the carrier protein and the polysaccharide antigen can be effectively prevented from being excessively crosslinked. Further, particle size distribution of the conjugate is significantly uniform and controllable, which provides an effective means for improving quality of a polysaccharide-protein conjugate vaccine.