Streptococcus agalactiae or Group B Streptococcus (GBS) is a major causative agent of neonatal sepsis, meningitis, still births and postnatal complications in women. Capsular polysaccharides (CPS) on the bacterial surface are implicated in pathogen virulence by evasion of host cellular defense mechanisms and have in turn served as attractive vaccine candidates for maternal immunization. In this study, we probed the role of a key structural feature, N-acetylation of constituent sugars in GBS capsular polysaccharide, on product characteristics and preclinical immunogenicity. Loss of N-acetyl groups in CPS during the purification stage requires a re-N-acetylation step to restore the N-acetylation levels in the polysaccharide. GBS serotype (ST) III CPS with different % N-acetylation levels were prepared and utilized for conjugate vaccine preparation involving rCRM197 as a carrier protein and subjected to structural and analytical characterization and immunogenicity evaluation in rabbits. Although different levels of re-N-acetylation in CPS as determined by proton NMR did not impact glycoconjugate stability, serological analysis revealed strong and direct correlation of N-acetylation levels in the CPS to the quality of neutralizing (IgG) and functional antibody responses to the GBS III vaccine. Collectively, the study findings suggest N-acetylation to be a salient structural feature and part of the immunodominant epitope in GBS CPS that defines the critical product attributes dictating vaccine quality and immunogenicity.
扫码关注我们
求助内容:
应助结果提醒方式:
