Protective immune responses to meningococcal C conjugate vaccine after intranasal immunization of mice with the LTK63 mutant plus chitosan or trimethyl chitosan chloride as novel delivery platform.
Chitosan and its derivative N-trimethyl chitosan chloride (TMC), given as microparticles or powder suspensions, and the non-toxic mucosal adjuvant LTK63, were evaluated for intranasal immunization with the group C meningococcal conjugated vaccine (CRM-MenC). Mice immunized intranasally with CRM-MenC formulated with chitosan or TMC and the LTK63 mutant, showed high titers of serum and mucosal antibodies specific for the MenC polysaccharide. Neither significant differences were observed between microparticle formulations and powder suspensions nor when LTK63 was pre-associated to the delivery system or not. The bactericidal activity measured in serum of mice immunized intranasally with the conjugated vaccine formulated with the delivery systems and the LT mutant was superior to the activity in serum of mice immunized sub-cutaneously. Importantly, intranasal but not parenteral immunization, induced bactericidal antibodies at the nasal level, when formulated with both delivery system and adjuvant.
Baudner
Barbara C
BC
Leiden/Amsterdam Center for Drug Research, University of Leiden, The Netherlands. barbara_baudner@chiron.com
Verhoef
J Coos
JC
Giuliani
Marzia M
MM
Peppoloni
Samuele
S
Rappuoli
Rino
R
Del Giudice
Giuseppe
G
Junginger
Hans E
HE
D000281:Administration, Intranasal; D000818:Animals; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D016503:Drug Delivery Systems / Q000379:methods*; D004768:Enterotoxins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D029968:Escherichia coli Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005260:Female; D007114:Immunization; D022401:Meningococcal Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D010316:Particle Size
D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D022401:Meningococcal Vaccines; C118071:N-trimethyl chitosan chloride; C410218:serogroup C meningococcal conjugate vaccine; D048271:Chitosan; C027538:heat-labile enterotoxin, E coli