Immunochemical characteristics of Streptococcus pneumoniae type 3 capsular polysaccharide glycoconjugate constructs correlate with its immunogenicity in mice model

Abstract

A panel of derivatives were prepared from Streptococcus pneumoniae polysaccharide type 3 (Ps3) modified with adipic acid dihydrazide (ADH). The degree of coupling between Ps3-adh derivatives and diphtheria (DTd) or tetanus (TTd) toxoids was varied by ADH linker loading. A series of Ps3 derivatives and the resultant glycoconjugates (GC) were tested for their immunochemical activity in an ELISA. Antigenic properties of components in GCs were estimated by interaction with serotype-specific and toxin-neutralizing antibodies to confirm the preservation of native protective epitopes both of Ps3 and DTd. After immunization of mice, a correlation was established between immunochemical activity and immunogenicity of these GCs. A correlation model developed for Ps3-DTd conjugates allowed to predict the immunogenicity of similar design Ps3-TTd conjugates based on ELISA testing data. The plausibility of this prediction was confirmed by the test immunization of mice with Ps3-TTds. The proposed immunochemical approach to the assessment and control of native structural and functional antigenic elements in GCs is important for the optimization of vaccine design and is an adequate alternative to extensive physicochemical characterization for assessing immunogenicity.