Supplementary Materials

Supplementary Material for:

A semisynthetic Streptococcus pneumoniae serotype 8 glycoconjugate vaccine

Benjamin Schumann, Heung Sik Hahm, Sharavathi G. Parameswarappa, Katrin Reppe, Annette Wahlbrink, Subramanian Govindan, Paulina Kaplonek, Liise-anne Pirofski, Martin Witzenrath, Chakkumkal Anish, Claney L. Pereira*, Peter H. Seeberger*

*Corresponding author. Email: peter.seeberger{at}mpikg.mpg.de (P.H.S.); claneylebev.pereira{at}vaxxilon.com (C.L.P.)

Published 8 March 2017, Sci. Transl. Med. 9, eaaf5347 (2017)
DOI: 10.1126/scitranslmed.aaf5347

This PDF file includes:

  • Methods
  • Fig. S1. AGA of tetrasaccharides 1 to 4.
  • Fig. S2. Differential immune recognition of synthetic ST8 CPS frameshifts.
  • Fig. S3. Solution-phase syntheses of ST8 CPS frameshift C(12) and disaccharide 13.
  • Fig. S4. Characterization of the CRM197–frameshift C(12) glycoconjugate.
  • Fig. S5. Time course of antiglycan immune responses after immunization with CRM197–frameshift C(12).
  • Fig. S6. Characterization of mAbs raised against ST8 frameshift C(12).
  • Fig. S7. Binding of ST8-related glycans by mAbs 1H8, 28H11, and 1F1.
  • Fig. S8. Qualitative comparison of binding kinetics of mAb 1H8 toward ST8 CPS–derived glycans of different chain lengths.
  • Fig. S9. Correlation between mAb 1H8 levels and bacterial burden in blood after passive immunization and lethal pneumococcal challenge.
  • Fig. S10. Divergent total syntheses of ST8 frameshift C–related glycans 21 to 24 from versatile precursor 32.
  • Fig. S11. Total synthesis of ST8 tetrasaccharide 15.
  • Fig. S12. Binding characterization of mAbs 1H8 and 1F1 to ST8 CPS–derived substructures by glycan microarray.
  • Fig. S13. Determination of affinities of mAb 1H8 toward synthetic ST8 CPS–related oligosaccharides.
  • Fig. S14. Conjugation of synthetic oligosaccharides to CRM197 using the bifunctional spacer bis(4-nitrophenyl)adipate (DNAP).
  • Fig. S15. Evaluation of CRM197 glycoconjugates of trisaccharide 21 and tetrasaccharide 22 in mice.
  • Fig. S16. Immune response against semisynthetic ST8 glycoconjugates in rabbits.
  • Fig. S17. Adsorption of ST8 glycoconjugates to Prevnar 13, as assessed by flow cytometry.
  • Fig. S18. Effect of coformulation of semisynthetic ST8 glycoconjugates with Prevnar 13 on the immune response against several pneumococcal CPSs.
  • Table S1. Sequences of automated assembly of protected ST8 CPS–related tetrasaccharide frameshifts.
  • Table S2. Antipolysaccharide IgG end point titers of rabbits immunized with Prevnar 13 alone or coformulated with semisynthetic ST8 glycoconjugates.
  • Spectra
  • References (3945)

[Download PDF]