A Semi-synthetic Oligosaccharide Conjugate Vaccine Candidate Confers Protection against Streptococcus pneumoniae Serotype 3 Infection.
The identification of immunogenic glycotopes that render glycoconjugate vaccines protective is key to improving vaccine efficacy. Synthetic oligosaccharides are an attractive alternative to the heterogeneous preparations of purified polysaccharides that most marketed glycoconjugate vaccines are based on. To investigate the potency of semi-synthetic glycoconjugates, we chose the least-efficient serotype in the current pneumococcal conjugate vaccine Prevnar 13, Streptococcus pneumoniae serotype 3 (ST3). Glycan arrays containing synthetic ST3 repeating unit oligosaccharides were used to screen a human reference serum for antibodies and to define the recognition site of two ST3-specific protective monoclonal antibodies. The glycan array screens identified a tetrasaccharide that was selected for in-depth immunological evaluation. The tetrasaccharide-CRM197 carrier protein conjugate elicited protective immunity as evidenced by opsonophagocytosis assays and protection against pneumonia caused by ST3 in mice. Formulation of the defined protective lead candidate glycotope has to be further evaluated to elicit optimal long-term immunity.
Department of Biomolecular Systems, Max-Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany.
Sharavathi Guddehalli
SG
Parameswarappa
Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany.
Katrin
K
Reppe
Department of Biomolecular Systems, Max-Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany; Institute of Chemistry and Biochemistry, Freie Universität Berlin, Arnimallee 22, 14195 Berlin, Germany.
Andreas
A
Geissner
Department of Biomolecular Systems, Max-Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany.
Petra
P
Ménová
Department of Biomolecular Systems, Max-Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany.
Subramanian
S
Govindan
Department of Biomolecular Systems, Max-Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany.
Adam D J
ADJ
Calow
Department of Biomolecular Systems, Max-Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany.
Annette
A
Wahlbrink
Department of Biomolecular Systems, Max-Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany; Institute of Chemistry and Biochemistry, Freie Universität Berlin, Arnimallee 22, 14195 Berlin, Germany.
Markus W
MW
Weishaupt
Department of Biomolecular Systems, Max-Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany; Institute of Chemistry and Biochemistry, Freie Universität Berlin, Arnimallee 22, 14195 Berlin, Germany.
Bopanna Ponnappa
BP
Monnanda
Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany.
Roland Lawrence
RL
Bell
Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY 10461, USA; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Liise-Anne
LA
Pirofski
Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany.
Norbert
N
Suttorp
Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany.
Leif Erik
LE
Sander
Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany. Electronic address: martin.witzenrath@charite.de.
Martin
M
Witzenrath
Department of Biomolecular Systems, Max-Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany.
Claney Lebev
CL
Pereira
Department of Biomolecular Systems, Max-Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany.
Chakkumkal
C
Anish
Department of Biomolecular Systems, Max-Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany; Institute of Chemistry and Biochemistry, Freie Universität Berlin, Arnimallee 22, 14195 Berlin, Germany. Electronic address: peter.seeberger@mpikg.mpg.de.
Peter H
PH
Seeberger
D000818:Animals; D002460:Cell Line; D005260:Female; D006801:Humans; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D009844:Oligosaccharides / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*
C538862:13-valent pneumococcal vaccine; D009844:Oligosaccharides; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate
Epitope mapping; Glycan arrays; Glycoconjugate vaccines; Opsonophagocytosis; Streptococcus pneumoniae; Synthetic glycans