Intranasal immunization with influenza vaccine and a detoxified mutant of heat labile enterotoxin from Escherichia coli (LTK63).
Groups of 10 Balb/c mice were immunized intranasally (IN) with influenza haemagglutinin (HA), and a genetically detoxified mutant of heat-labile enterotoxin from Escherichia coli (LTK63) at several different doses. IN immunization at the optimal dose combination for HA and LTK63 induced equivalent levels of serum IgG antibodies to intramuscular (IM) immunization with HA alone, and induced significantly enhanced IgA titers in nasal wash. However, haemagglutination inhibition (HI) assays showed that the IM vaccine induced approximately 10-fold higher HI titers than IN immunization with HA and LTK63. In a second study, HA and LTK63 was compared to a licensed emulsion adjuvant MF59 by the IN route. LTK63 was shown to be significantly more potent than MF59 when evaluated at the optimal dose combination with HA. Hence, the LTK63 and HA combination represents an attractive candidate for evaluation as an IN vaccine in larger animal models, or humans.
Pine
Samuel
S
Chiron Corporation, 5300 Chiron Way, Emeryville, CA 94068, USA.
Barackman
John
J
Ott
Gary
G
O'Hagan
Derek
D
D000281:Administration, Intranasal; D000818:Animals; D001427:Bacterial Toxins / Q000008:administration & dosage* / Q000235:genetics* / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004768:Enterotoxins / Q000008:administration & dosage* / Q000235:genetics* / Q000276:immunology; D004926:Escherichia coli / Q000235:genetics / Q000276:immunology*; D029968:Escherichia coli Proteins; D005260:Female; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000097:blood; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D014611:Vaccination / Q000379:methods*
D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; C027538:heat-labile enterotoxin, E coli