Efficacy of intradermal trivalent influenza vaccine with topical imiquimod, a potent synthetic toll-like receptor 7 agonist

Abstract

BACKGROUND: Imiquimod, a synthetic Toll-like receptor 7 (TLR7) agonist, has been shown to enhance immunogenicity as adjuvant to influenza vaccine delivered by microneedles in mouse model. We hypothesized that topical imiquimod before intradermal influenza vaccination will produce similar effect in human. METHODS: We performed a prospective double-blind randomized controlled trial on chronically ill adults. Subjects were randomly assigned into 3 groups. Participants in both the experimental (IQ) and control group (INT) received a single dose of intradermal trivalent influenza vaccine (Intanza®15, Sanofi-Pasteur, France). In the IQ group, 5% 250mg imiquimod ointment was applied to the dermal site of injection 5 minutes before vaccination. In the INT group, aqueous cream was applied instead. In the other control group (IM), participants received a similar dose of intramuscular influenza vaccine (Vaxigrip®, Sanofi-Pasteur, France) with aqueous cream applied to the dermal site. Both patients and investigators were blinded to the type of topical treatment applied. We measured antibody titres by hemagglutination inhibition (HAI) and microneutralization (MN) assays at baseline, day 7, 14 and 21 after vaccination. The primary outcome measure is the immunogenicity by seroconversion rate on day 7 after vaccination. RESULTS: Baseline characteristics for all groups were similar (IQ=28; IM=27; INT=29). Seroconversion rate in all 3 strains was significantly higher in the IQ group than the two controls (p≤0.001) on day 7, 14 and 21. Seroprotection rate and GMT fold increase in the H1N1 strain was also significantly higher in the IQ group than the two controls (p<0.05) on day 7, 14 and 21. The GMT in all three strains at any time point was higher in the IQ group. Strong correlation was found between post-vaccination site redness and day 7 immunogenicity. No serious adverse events were reported. CONCLUSION: Pretreatment with topical imiquimod expedite and augment the immunogenicity of intradermal influenza vaccination.