Exploration of Recombinant Fusion Proteins YAPO and YAPL as Carrier Proteins for Glycoconjugate Vaccine Design against Streptococcus pneumoniae Infection

Abstract

Pneumolysin (Ply), pneumococcal surface protein A (PspA), and pneumococcal surface adhesin A (PsaA) are promising cell surface protein antigen targets for Streptococcus pneumoniae (Spn) vaccine development. Herein, we designed and recombined two fusion proteins, named YAPO and YAPL, which contained the main antigenic epitopes of Ply, PspA, and PsaA. In-depth immunological evaluations revealed that YAPO and YAPL had strong immunocompetence to be well-qualified potential carrier proteins. To verify this possibility, a serotype 3 Spn (ST3) CPS pentasaccharide was conjugated to both fusion proteins, respectively, to generate the resultant glycoconjugates. Immunological studies in mice disclosed, as compared with TT conjugate, YAPO and YAPL conjugates provoked robust T-cell dependent immune responses that could provide better recognition, in vitro efficient opsonophagocytosis and in vivo effective protection against various serotypes of Spn. Collectively, YAPO and YAPL were identified as immunopotentiating carriers that could help convert immunologically inactive ST3 pentasaccharide into a T cell-dependent antigen and provide efficient and broad spectrum of immunoprotection coverage so as to formulate functional glycoconjugate vaccines against Spn infections.