Preclinical studies on new proteins as carrier for glycoconjugate vaccines

• Published in: Vaccine Vol. 34; no. 35; pp. 4235 - 4242
• Main Authors: Tontini, M, Romano, M.R, Proietti, D, Balducci, E, Micoli, F, Balocchi, C, Santini, L, Masignani, V, Berti, F, Costantino, P
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 29-07-2016; Elsevier Limited
• Subjects: Allergy and Immunology; Animals; Antibodies, Bacterial - blood; Antibody Formation; Antigens; Candidates; Carrier protein; Carrier Proteins - chemistry; Chromatography; CRM197; Diphtheria; E coli; Genomes; Glucans - chemistry; Glycoconjugates; Glycoconjugates - chemistry; Haemophilus influenzae; Immunogenicity; Immunogenicity, Vaccine; Licenses; Manufacturing; Meningococcal vaccines; Mens health; Mice; Mice, Inbred BALB C; Neisseria meningitidis; Neisseria meningitidis, Serogroup C; Polysaccharides, Bacterial - immunology; Proteins; Recombinant Proteins - chemistry; Research centers; Saccharides; Serum Bactericidal Antibody Assay; Streptococcus infections; Streptococcus pneumoniae; Tetanus; Toxins; Vaccines; Vaccines, Conjugate - chemistry; Vaccines, Conjugate - immunology; Italy; Meningococcal vaccines; Glycoconjugates; CRM 197; Carrier protein; CRM197; CRM
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2016.06.039

Abstract Glycoconjugate vaccines are made of carbohydrate antigens covalently bound to a carrier protein to enhance their immunogenicity. Among the different carrier proteins tested in preclinical and clinical studies, five have been used so far for licensed vaccines: Diphtheria and Tetanus toxoids, the non-toxic mutant of diphtheria toxin CRM197 , the outer membrane protein complex of Neisseria meningitidis serogroup B and the Protein D derived from non-typeable Haemophilus influenzae . Availability of novel carriers might help to overcome immune interference in multi-valent vaccines containing several polysaccharide-conjugate antigens, and also to develop vaccines which target both protein as well saccharide epitopes of the same pathogen. Accordingly we have conducted a study to identify new potential carrier proteins. Twenty-eight proteins, derived from different bacteria, were conjugated to the model polysaccharide Laminarin and tested in mice for their ability in inducing antibodies against the carbohydrate antigen and eight of them were subsequently tested as carrier for serogroup meningococcal C oligosaccharides. Four out of these eight were able to elicit in mice satisfactory anti meningococcal serogroup C titers. Based on immunological evaluation, the Streptococcus pneumoniae protein spr96/2021 was successfully evaluated as carrier for serogroups A, C, W, Y and X meningococcal capsular saccharides.