Immunogenicity of conjugate vaccines consisting of pneumococcal capsular polysaccharide types 6B, 14, 19F, and 23F and a meningococcal outer membrane protein complex

Abstract

In an effort to prepare pneumococcal (Pn) capsular polysaccharide (Ps) vaccines that would be immunogenic in infants, covalent conjugates were prepared for Pn types 6B, 14, 19F, and 23F. Each Ps type was covalently bound to an outer membrane protein complex from Neisseria meningitidis serogroup B and evaluated for immunogenicity in mice and infant monkeys. The conjugates induced specific anti-Ps antibody responses in mice and in infant rhesus and African green monkeys; a coniugate of 6B and outer membrane protein complex was immunogenic at Ps doses as low as 20 ng. Although low levels of the Pn group-common cell wall polysaccharide were present in all type-specific Ps preparations, anti-cell wall polysaccharide responses induced by covalent conjugates were < 1% of the total anti-Ps response after two doses of vaccine. In contrast, the anti-cell wall polysaccharide response of a noncovalent conjugate represented 41% of the anti-Ps response after two doses. Relative T-cell dependence, a requirement for the human target population of infants less than 18 months old, was demonstrated for all four Pn Ps con,jugates in an athymic mouse model. Therefore, these Pn Ps-outer membrane protein complex conjugate vaccines are excellent candidates for evaluation in human infants.

Dynamics of the Murine Humoral Immune Response toNeisseria meningitidisGroup B Capsular Polysaccharide

“…On the other hand, our results emphasize the critical importance of incorporating components that complement and amplify the CpsB-initiated response. The outer membrane vesicles have these properties (9,31,50,53). However, their composition must have major effects on the response.…”

Carbohydrate based vaccines

“…Proteins that have been applied to couple with carbohydrates are e.g. tetanus and diphtheria toxoids, crossreactive material of diphtheria toxoid (CRM 197 ) [9], key hole limpet hemocyanin (KLH) and the outer membrane complex of Neisseria meningitides [10]. A few other bacteria-derived proteins were so far studied in the laboratory, only.…”

Conjugate vaccines

“…Primary antibody responses to the Hib conjugate vaccines in infancy have been demonstrated to be predominantly IgG1 [20], while boosting with pure PRP in toddlers generates a response that is dominated by IgG1 although IgG2 responses are also seen [21]. Adult responses to pneumococcal polysaccharides are dominated by IgG2, but both IgG1 and IgG2 are mounted to pneumococcal conjugate vaccines in adults [22, 23].…”