Study of Various Presentation Forms for a Peptide Mimetic of Neisseria meningitidis Serogroup B Capsular Polysaccharide

• Published in: Bioconjugate chemistry 2011-01, Vol.22 (1), p.33-41
• Main Authors: Garay, Hilda, Menéndez, Tamara, Cruz-Leal, Yoelys, Coizeau, Edelgis, Noda, Jesus, Morera, Vivian, Guillén, Gerardo, Albericio, Fernando, Reyes, Osvaldo
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antigen Presentation; Antigens; Bacterial Capsules - chemistry; Bacterial Capsules - immunology; Biochemistry; Carbohydrates; Dose-Response Relationship, Immunologic; Drug Design; Female; Gram-negative bacteria; Immunoglobulin G - biosynthesis; Immunoglobulin G - immunology; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Monoclonal antibodies; Neisseria meningitidis, Serogroup B; Peptides; Peptidomimetics - chemistry; Peptidomimetics - immunology; Protein Multimerization; Protein Structure, Quaternary; Serum Bactericidal Antibody Assay
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/bc100299g

The formulation of a broadly protective vaccine to prevent the serogroup B Neisseria meningitidis (MenB) disease is still an unmet medical need. We have previously reported the induction of bactericidal and protective antibodies against MenB after immunization of mice with a phage-displayed peptide named 4 L-5. This peptide mimics a capsular polysaccharide (CPS) epitope in MenB. With the aim of developing vaccine formulations that could be used in humans, we evaluate in this study various forms of presentation to the immune system of the 4 L-5 sequence, based on synthetic peptides. We synthesized the following: (i) a linear 4 L-5 peptide, (ii) a multiple antigen peptide containing four copies of the 4 L-5 sequence (named MAP), which was then dimerized, and the product named dimeric MAP, and (iii) a second multiple antigen peptide, in this case with two copies of the 4 L-5 sequence and a copy of a T-helper cell epitope of tetanus toxoid, which was then dimerized and the product named MAP-TT. The linear peptide, the MAP, and the dimeric MAP were conjugated to the carrier protein P64K by different conjugation methods. Plain antigens and antigens coupled to P64K were used to immunize BALB/c mice. Of those variants that gave immunogenic results, MAP-TT rendered the highest levels of specific antipeptide IgG antibodies and serum bactericidal activity. These results can find application in the development of meningococcal vaccine candidates and in peptide-based vaccines strategies.