Design of a liposomal candidate vaccine against Pseudomonas aeruginosa and its evaluation in triggering systemic and lung mucosal immunity.
OBJECTIVE
To design and evaluate liposomal constructs capable of inducing a potent systemic and airway humoral response to Pseudomonas aeruginosa


METHODS
Liposomes contained a peptide derived from P. aeruginosa pilin protein as B epitope, a peptide derived from Influenza hemagglutinin protein as Th epitope, the TLR agonist Pam3CAG or Pam2CAG as adjuvant, and a mannosylated lipid as dendritic cell targeting agent. These constructions were administered to mice intraperitoneally (i.p.) or intranasally (i.n.). Their immunogenicity was evaluated by measuring B epitope-specific immunoglobulins in the serum and the airways by ELISA.


RESULTS
The B epitope, in its native form or after substitution of a cysteine by a serine, induced high systemic IgG titers when formulated in the presence of Pam3CAG or Pam2CAG and administered i.p.. No IgA response was observed in the airways upon injection of candidate vaccines by i.p. route, whatever the B epitope or the adjuvant. However, i.n. vaccination resulted in a significant local production of IgA. Finally, the production of IgG was more rapid when mannose was incorporated.


CONCLUSIONS
All liposomal candidate vaccines tested induced the production of IgG and/or IgA directed against an immunogenic peptide from P. aeruginosa. Liposomal constructs could be attractive in the vaccination against P. aeruginosa.
Heurtault
Béatrice
B
Laboratoire de Chimie Enzymatique et Vectorisation, Université Louis Pasteur, Institut Gilbert Laustriat, CNRS-UMR 7175, Faculté de Pharmacie, 74 route du Rhin, BP 60024, 67401, Illkirch Cedex, France. heurtault@bioorga.u-strasbg.fr
Gentine
Philippe
P
Thomann
Jean-Sébastien
JS
Baehr
Corinne
C
Frisch
Benoît
B
Pons
Françoise
F
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D015195:Drug Design; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D018928:Immunity, Mucosal; D007115:Immunization Schedule; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007274:Injections, Intraperitoneal; D008074:Lipoproteins / Q000276:immunology; D008081:Liposomes; D008168:Lung / Q000276:immunology*; D008297:Male; D008358:Mannose / Q000031:analogs & derivatives / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010088:Oxidoreductases / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D054406:Pseudomonas Vaccines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology*; D013997:Time Factors
D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008074:Lipoproteins; D008081:Liposomes; D010446:Peptide Fragments; D054406:Pseudomonas Vaccines; C081942:influenza hemagglutinin (307-319); C061110:N-palmitoyl-5,6-dipalmitoylcysteinyl-alanyl-glycine; D010088:Oxidoreductases; C068255:pilB protein, Bacteria; D008358:Mannose
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