The present invention describes a combined vaccine that offers broad protection against meningococcal disease caused by the pathogenic bacteria Neisseria meningitidis. The vaccine is comprised of four distinct polysaccharide-protein conjugates that are formulated as a single dose of vaccine. Purified capsular polysaccharides from Neisseria meningitidis serogroups A, C, W-135, and Y are chemically activated and selectively attached to a carrier protein by means of a covalent chemical bond, forming polysaccharide-protein conjugates capable of eliciting long-lasting immunity to a variety of N. meningitidis strains in children as well as adults.

Provided are a protein antigen subjected to site-directed mutation and site-directed modification, and a method for site-directed mutation and site-directed modification of the protein antigen. The method comprises: site-directedly introducing an unnatural amino acid into a specific site of the protein antigen by genetic codon expansion technique; and performing site-directed modification with the protein antigen by the unnatural amino acid and a modifier, wherein the modifier is a receptor agonist such as tripalmitoyl-S-glyceryl cysteine and monophosphoryl lipid A. Further provided is use of the protein antigen subjected to site-directed mutation and site-directed modification, such as use as a vaccine.

Provided are a protein antigen subjected to site-directed mutation and site-directed modification, and a method for site-directed mutation and site-directed modification of the protein antigen. The method comprises: site-directedly introducing an unnatural amino acid into a specific site of the protein antigen by genetic codon expansion technique; and performing site-directed modification with the protein antigen by the unnatural amino acid and a modifier, wherein the modifier is a receptor agonist such as tripalmitoyl-S-glyceryl cysteine and monophosphoryl lipid A. Further provided is use of the protein antigen subjected to site-directed mutation and site-directed modification, such as use as a vaccine.

The present invention relates to a complex of polyproteins containing immunogenic regions derived from the P36, P46, HSP, NrdF, P97, MHP271 e P216 antigens of M. hyopneumoniae, which regions are fused with segments of the Rrp4. Rrp41 and Rrp42 carrier proteins of P. abyssi, forming a single complex. The present invention further provide the following objects: (i) a gene coding the polyprotein complex, which complex is based on the exosome of P. abyssi and carries copies of vaccine antigens of M. hyopneumoniae; (ii) an antigenic composition comprising the polyprotein complex of the invention, optionally one or more auxiliary agents and/or additives and a pharmacologically acceptable excipient; (iii) a method for producing said polyprotein complex; and (iv) uses of said complex and composition in the treatment and prevention of disease caused by M. hyopneumoniae infection.

The invention is directed to multivalent pneumococcal glycoconjugate compositions containing a newly emerging serotype of S. pneumonia, polysaccharide 24F, and their manufacture and use. The pneumococcal serotype 24F contains a polysaccharide repeating unit structure. The multivalent immunogenic composition comprises at least 25 S. pneumonia capsular polysaccharides selected from the serotypes 1, 2, 3, 4, 5, 6B, 6C, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15A, 15B, 15C, 16F, 17F, 18C, 19A, 19F, 20, 22F, 23B, 23F, 24F, 33F and 35B of S. pneumoniae preferably conjugated to carrier protein either directly or through a linker and a pharmaceutically acceptable carrier and/or adjuvant. The disclosure provides the capsular polysaccharide structure of serotype 24F to understand the polysaccharide before conjugation with carrier protein.

The invention is directed to multivalent pneumococcal glycoconjugate compositions containing a newly emerging serotype of S. pneumonia, polysaccharide 24F, and their manufacture and use. The pneumococcal serotype 24F contains a polysaccharide repeating unit structure. The multivalent immunogenic composition comprises at least 25 S. pneumonia capsular polysaccharides selected from the serotypes 1, 2, 3, 4, 5, 6B, 6C, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15A, 15B, 15C, 16F, 17F, 18C, 19A, 19F, 20, 22F, 23B, 23F, 24F, 33F and 35B of S. pneumoniae preferably conjugated to carrier protein either directly or through a linker and a pharmaceutically acceptable carrier and/or adjuvant. The disclosure provides the capsular polysaccharide structure of serotype 24F to understand the polysaccharide before conjugation with carrier protein.

The present application discloses an immunogenic composition comprising N. meningitidis capsular polysaccharides from at least one of serogroups A, C, W135 and Y conjugated to a carrier protein to produce a N. meningitidis capsular polysaccharide conjugate, wherein the average size of each N. meningitidis polysaccharide is above 50 kDa.

The present application discloses an immunogenic composition comprising N. meningitidis capsular polysaccharides from at least one of serogroups A, C, W135 and Y conjugated to a carrier protein to produce a N. meningitidis capsular polysaccharide conjugate, wherein the average size of each N. meningitidis polysaccharide is above 50 kDa.

Provided are mixed carrier, multivalent pneumococcal conjugate compositions comprising 20 different pneumococcal capsular polysaccharide-protein conjugates, wherein each of the conjugates includes a capsular polysaccharide from a different serotype of Streptococcus pneumoniae conjugated to either tetanus toxoid or CRM.sub.197, wherein the Streptococcus pneumoniae serotypes are selected from 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F, wherein two of the capsular polysaccharides are conjugated to tetanus toxoid and the remaining capsular polysaccharides are conjugated to CRMig7, and wherein the two capsular polysaccharides that are conjugated to tetanus toxoid are selected from the group consisting of serotypes 1, 3, and 5. Also provided are methods of producing the mixed carrier, multivalent pneumococcal conjugate compositions and methods of using the same for prophylaxis against Streptococcus pneumoniae infection or disease in a subject.

Provided are mixed carrier, multivalent pneumococcal conjugate compositions comprising 20 different pneumococcal capsular polysaccharide-protein conjugates, wherein each of the conjugates includes a capsular polysaccharide from a different serotype of Streptococcus pneumoniae conjugated to either tetanus toxoid or CRM.sub.197, wherein the Streptococcus pneumoniae serotypes are selected from 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F, wherein two of the capsular polysaccharides are conjugated to tetanus toxoid and the remaining capsular polysaccharides are conjugated to CRMig7, and wherein the two capsular polysaccharides that are conjugated to tetanus toxoid are selected from the group consisting of serotypes 1, 3, and 5. Also provided are methods of producing the mixed carrier, multivalent pneumococcal conjugate compositions and methods of using the same for prophylaxis against Streptococcus pneumoniae infection or disease in a subject.