Gold nanoparticles as carriers for a synthetic Streptococcus pneumoniae type 14 conjugate vaccine.
OBJECTIVE
Coupling of capsular polysaccharides of pathogens to immunogenic protein carriers (conjugate vaccines) improves carbohydrate immune response. Our idea is to explore gold nanoclusters as carriers to prepare fully synthetic carbohydrate vaccines.


METHODS
Gold glyconanoparticles bearing a synthetic tetrasaccharide epitope related to the Streptococcus pneumoniae type 14 capsular polysaccharide (Pn14PS), the T-helper ovalbumin 323-339 peptide (OVA(323-339)), and D-glucose were prepared by a one-pot method. Their immunogenicity was tested in mice. Cytokine levels after spleen cell stimulation with OVA(323-339) were analyzed using a luminex-multiplex cytokine assay. The capacity of the evoked antibodies to promote the uptake of S. pneumoniae type 14 by leukocytes was assessed.


CONCLUSIONS
Glyconanoparticles containing 45% of tetrasaccharide and 5% OVA(323-339) triggered specific anti-Pn14PS IgG antibodies. Cytokine levels confirmed that glyconanoparticles led to T-helper cell activation. The anti-saccharide antibodies promoted the phagocytosis of type 14 bacteria by human leukocytes, indicating the functionality of the antibodies.


CONCLUSIONS
Gold nanoparticles have great potential as carriers for the development of a great diversity of fully synthetic carbohydrate-based vaccines.
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Dodi
D
Safari
Marco
M
Marradi
Fabrizio
F
Chiodo
Huberta A
HA
Th Dekker
Yulong
Y
Shan
Roberto
R
Adamo
Stefan
S
Oscarson
Ger T
GT
Rijkers
Martina
M
Lahmann
Johannis P
JP
Kamerling
Soledad
S
Penadés
Harm
H
Snippe
D000818:Animals; D016667:Bacterial Capsules / Q000737:chemistry / Q000276:immunology; D001428:Bacterial Vaccines / Q000737:chemistry / Q000276:immunology; D002241:Carbohydrates / Q000737:chemistry / Q000276:immunology; D016503:Drug Delivery Systems; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006046:Gold / Q000737:chemistry; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010587:Phagocytosis; D013296:Streptococcus pneumoniae / Q000737:chemistry / Q000276:immunology; D018074:Vaccines, Conjugate / Q000737:chemistry / Q000276:immunology
D001428:Bacterial Vaccines; D002241:Carbohydrates; D000939:Epitopes; D018074:Vaccines, Conjugate; D006046:Gold