Immunogenicity in a mouse model of a conjugate vaccine made with a synthetic single repeating unit of type 14 pneumococcal polysaccharide coupled to CRM197.
Oligosaccharides (OSs) related to the pneumococcal type 14 capsular polysaccharide (Pn14PS) were studied for their ability to inhibit the binding between anti-PS14 antisera and native PS14. A synthetic tetrasaccharide corresponding to the repeating unit of the Pn14PS, a hexasaccharide mimic, and an octasaccharide fragment obtained by Pn14PS depolymerization were good inhibitors. CRM197 conjugates of the tetrasaccharide and an octasaccharide mimic were prepared by using either adipic acid diester or diethyl squarate linkers. The conjugate with the tetrasaccharide chains induced anti-Pn14PS antibodies when injected subcutaneously into mice, as determined by an enzyme-linked immunosorbent assay, and antibody titers increased with oligosaccharide loading. The adipic acid-linked tetrasaccharide conjugates elicited higher antibody titers than those prepared with a squarate spacer. The lower anti-Pn14PS antibody response of the octasaccharide mimic conjugate indicates the importance of the backbone galactose residue for an appropriate antibody response. The OS-CRM197 conjugate prepared from a single repeat unit of the Pn14PS is a potential vaccine candidate.
Division of Bacteriology, National Institute for Biological Standards and Control, South Mimms, Potters Bar, Herts EN6 3QG, United Kingdom. fmawas@nibsc.ac.uk
Fatme
F
Mawas
Jutta
J
Niggemann
Christopher
C
Jones
Michael J
MJ
Corbel
Johannis P
JP
Kamerling
Johannes F G
JF
Vliegenthart
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D016667:Bacterial Capsules / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology*; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology*; D002240:Carbohydrate Sequence; D002352:Carrier Proteins / Q000008:administration & dosage / Q000737:chemistry; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000737:chemistry; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; D009844:Oligosaccharides; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate; D014614:Vaccines, Synthetic; C056696:pneumococcal polysaccharide, type 14; C028581:CRM197 (non-toxic variant of diphtheria toxin)