Evaluation of a Group A Streptococcus synthetic oligosaccharide as vaccine candidate.
Bacterial infections caused by Group A Streptococcus (GAS) are a serious health care concern that currently cannot be prevented by vaccination. The GAS cell-wall polysaccharide (GAS-PS) is an attractive vaccine candidate due to its constant expression pattern on different bacterial strains and protective properties of anti-GAS-PS antibodies. Here we report for the first time the immunoprotective efficacy of glycoconjugates with synthetic GAS oligosaccharides as compared to those containing the native GAS-PS. A series of hexa- and dodecasaccharides based on the GAS-PS structure were prepared by chemical synthesis and conjugated to CRM(197). When tested in mice, the conjugates containing the synthetic oligosaccharides conferred levels of immunoprotection comparable to those elicited by the native conjugate. Antisera from immunized rabbits promoted phagocytosis of encapsulated GAS strains. Furthermore we discuss variables that might correlate with glycoconjugate immunogenicity and demonstrate the potential of the synthetic approach that benefits from increased antigen purity and facilitated manufacturing.
Kabanova
Anna
A
Research Center, Novartis Vaccines and Diagnostics, Via Fiorentina 1, 53100 Siena, Italy.
Margarit
Immaculada
I
Berti
Francesco
F
Romano
Maria R
MR
Grandi
Guido
G
Bensi
Giuliano
G
Chiarot
Emiliano
E
Proietti
Daniela
D
Swennen
Erwin
E
Cappelletti
Emilia
E
Fontani
Paola
P
Casini
Daniele
D
Adamo
Roberto
R
Pinto
Vittoria
V
Skibinski
David
D
Capo
Sabrina
S
Buffi
Giada
G
Gallotta
Marilena
M
Christ
William J
WJ
Campbell
A Stewart
AS
Pena
John
J
Seeberger
Peter H
PH
Rappuoli
Rino
R
Costantino
Paolo
P
D000818:Animals; D005260:Female; D051379:Mice; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000276:immunology*; D010587:Phagocytosis; D011817:Rabbits; D044967:Serum / Q000276:immunology; D022541:Streptococcal Vaccines / Q000138:chemical synthesis / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
D009844:Oligosaccharides; D022541:Streptococcal Vaccines; D018074:Vaccines, Conjugate; D014614:Vaccines, Synthetic