Topical Imiquimod Does not Provide an Adjuvant Effect when Administered with Inactivated Influenza A/H5N1 Vaccine in Healthy Young Adults.

BACKGROUND: Safe, effective and easy to deploy adjuvants are needed for influenza pre-pandemic preparedness. Based on recent reports we hypothesized that pre-application of topical imiquimod followed by intradermal (ID) vaccination with monovalent inactivated influenza A/H5N1 vaccine (MIV A/H5N1) results in improved serologic responses.

METHODS: We randomized 50 healthy adults in a 1:1 ratio to receive topical imiquimod (Group 1) or control cream (Group 2) followed by ID injection of 9µg of the hemagglutinin (HA) MIV A/H5N1 in two doses, 21 days apart. Subjects were followed for safety and serologic responses as measured by the hemagglutination inhibition (HAI) and microneutralization (MN) assays.

RESULTS: Solicited and unsolicited adverse events were comparable between Groups 1 and 2, and were mostly mild to moderate in severity. At 21 days post dose 2, the geometric mean titers (GMTs) of HAI antibodies against the vaccine strain were 16.2 and 24.3 in Groups 1 and 2, respectively. The MN antibody GMTs were 9.3 and 10.7 in Groups 1 and 2, respectively. There were no significant differences in antibody levels between groups at study time points.

CONCLUSION: Topical imiquimod administration combined with ID MIV A/H5N1 was safe, but did not result in improved serologic responses to the vaccine.