Intranasal immunization of mice with influenza vaccine in combination with the adjuvant LT-R72 induces potent mucosal and serum immunity which is stronger than that with traditional intramuscular immunization

Abstract

Immunization of mice by the intranasal route with influenza virus hemagglutinin in combination with the mutant Escherichia coli heat-labile enterotoxin R72 (LT-R72) induced significantly enhanced serum and mucosal antibodies, surpassing, in most cases, responses achieved by traditional intramuscular immunization using inactivated split influenza vaccine. Furthermore, intranasal immunization with LT-R72 induced a potent serum immunoglobulin G2a response, indicating that this adjuvant has Th1 character.

FIG. 1

Comparison of the effects of i.m. and i.n. administrations of A/Beijing93 HA on antigen-specific serum antibody responses. Shown are mean anti-A/Beijing93 HA serum Ig antibody titers of groups of 10 mice immunized as shown in Table 1. Asterisks indicate groups whose values are significantly greater than those of the corresponding i.m. immunized group (P ≤ 0.05).

FIG. 2

Comparison of the effects of i.m. and i.n. administrations of a bivalent vaccine containing A/Beijing93 HA on serum HI titers. The data shown is for pooled serum from groups of 10 mice immunized as shown in Table 1.

FIG. 3

Comparison of the effects of i.m. and i.n. administrations of A/Beijing93 HA on antigen-specific IgA responses. Mean anti-A/Beijing93 HA IgA antibody titers of MW samples from groups of 10 mice immunized as shown in Table 1 (± 95% confidence intervals) are shown. Asterisks indicate groups whose titers are significantly greater than those of the corresponding i.m. immunized groups (P ≤ 0.05).

FIG. 4

Comparison of the effects of i.m. and i.n. administrations of A/Beijing93 HA on the ratio of antigen-specific IgG1 to IgG2a antibodies in the sera of groups of 10 mice immunized as shown in Table 1.