Topical Imiquimod Does Not Provide an Adjuvant Effect When Administered With Inactivated Influenza A/H5N1 Vaccine in Healthy Young Adults

Abstract

Background: Safe, effective, and easy to deploy adjuvants are needed for influenza prepandemic preparedness. Based on recent reports, we hypothesized that preapplication 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 9 µg of the hemagglutinin MIV A/H5N1 in 2 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 after 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.

Conclusions: Topical imiquimod administration combined with ID MIV A/H5N1 was safe but did not result in improved serologic responses to the vaccine.Clinical Trials Registration. NCT03472976.

Keywords: adjuvant; influenza; topical; vaccine.

© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Figures

Figure 1.

CONSORT diagram: disposition of study participants by group.

Figure 2.

A, Geometric mean titers of hemagglutination inhibition antibodies to the vaccine influenza A/H5N1 strain with corresponding 95% confidence intervals at all study time points. B, Geometric mean titers of neutralizing antibody to the vaccine influenza A/H5N1 strain with corresponding 95% confidence intervals, collected at all study time points.

Figure 3.

A, Geometric mean titers of hemagglutination inhibition antibodies to antigenically distinct influenza A/H5N1 strains with corresponding 95% confidence intervals, collected at baseline and 21 days after second vaccination. B, Geometric mean titers of neutralizing antibodies to 4 antigenically distinct influenza strains with corresponding 95% confidence intervals, collected at baseline and 21 days after second vaccination.