Design, characterization and preclinical efficacy of a cationic lipid adjuvant for influenza split vaccine.
We prepared a series of cationic lipid vesicles comprising a cationic cholesterol derivative, DC-Chol with or without a neutral phospholipid, DOPC or DOPE. The vesicles were tested for their ability to bind and adjuvant split inactivated influenza vaccines. We found that DC-Chol-containing liposomes are capable to strongly bind influenza vaccine antigens upon simple mixing with the vaccine. The resulting formulations induced robust anti-influenza immune responses both after s.c. and i.n. administration in BALB/c mice while neutral Cholesterol/DOPC liposomes displayed virtually no stable antigen binding and no adjuvant effect. The parenteral adjuvant effect of DC-Chol on trivalent split influenza vaccines was then confirmed in outbred mice and monkeys. Among the most potent formulations tested, a simple mixture of the vaccine with a microfluidized dispersion of DC-Chol in an aqueous buffer is being considered for further development to produce an improved influenza vaccine.
Guy
B
B
Aventis Pasteur, Campus Mérieux, 1541 Avenue Marcel Mérieux 69280, Marcy l'Etoile, France.
Pascal
N
N
Françon
A
A
Bonnin
A
A
Gimenez
S
S
Lafay-Vialon
E
E
Trannoy
E
E
Haensler
J
J
D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D021461:Animals, Outbred Strains; D000914:Antibodies, Viral / Q000276:immunology; D002412:Cations / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D002784:Cholesterol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005260:Female; D020404:Glycerophospholipids / Q000008:administration & dosage; D000882:Haplorhini / Q000276:immunology; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000096:biosynthesis; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010316:Particle Size; D010713:Phosphatidylcholines / Q000008:administration & dosage; D010714:Phosphatidylethanolamines; D055672:Static Electricity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D002412:Cations; D020404:Glycerophospholipids; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D008081:Liposomes; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C070648:3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol; D007371:Interferon-gamma; D002784:Cholesterol; C017251:1,2-oleoylphosphatidylcholine