title: Immunogenicity of intradermal trivalent influenza vaccine with topical imiquimod: a double blind randomized controlled trial.
abstract: BACKGROUND
  Imiquimod, a synthetic Toll-like receptor 7 agonist enhanced immunogenicity of influenza vaccine in a mouse model. We hypothesized that topical imiquimod before intradermal influenza vaccination (TIV) would produce similar effect in human.
  
  
  METHODS
  We performed a prospective 1-year follow-up, double-blind, randomized, controlled trial with adults with comorbidities. Participants were randomized to 1 of the following 3 vaccinations: topical 5% 250 mg imiquimod ointment followed by intradermal TIV, topical aqueous-cream followed by intradermal TIV, or topical aqueous-cream followed by intramuscular TIV. Patients and investigators were blinded to the type of topical treatment applied. Hemagglutination inhibition (HI) and microneutralization antibody titers were measured. The primary outcome was the day 7 seroconversion rate.
  
  
  RESULTS
  Ninety-one recruited participants completed the study. The median age was 73 years. On day 7, 27/30 (90%) patients who received imiquimod and intradermal TIV achieved seroconversion against the H1N1 strain by HI, compared with 4/30 (13.3%) who received aqueous-cream and intramuscular TIV (P < .001), and 12/31 (38.7%) who received aqueous-cream and intradermal TIV (P < .001). The seroconversion, seroprotection, and geometric mean titer-fold increase were met in all 3 strains in the imiquimod and intradermal TIV group 2 weeks earlier, and the better seroconversion rate was sustained from day 7 to year 1 (P ≤ .001). The better immunogenicity was associated with fewer hospitalizations for influenza or pneumonia (P < .05). All adverse reactions were self-limited.
  
  
  CONCLUSIONS
  Pretreatment with topical imiquimod significantly expedited, augmented, and prolonged the immunogenicity of influenza vaccination. This strategy for influenza immunization should be considered for the elderly population.
authors.affiliation: State Key Laboratory for Emerging Infectious Diseases, Carol Yu's Centre for Infection and Division of Infectious Diseases Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, China.
authors.forename: Ivan F N
authors.initials: IF
authors.lastname: Hung
authors.affiliation: State Key Laboratory for Emerging Infectious Diseases, Carol Yu's Centre for Infection and Division of Infectious Diseases.
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Zhang
authors.affiliation: State Key Laboratory for Emerging Infectious Diseases, Carol Yu's Centre for Infection and Division of Infectious Diseases.
authors.forename: Kelvin K W
authors.initials: KK
authors.lastname: To
authors.affiliation: State Key Laboratory for Emerging Infectious Diseases, Carol Yu's Centre for Infection and Division of Infectious Diseases.
authors.forename: Jasper F W
authors.initials: JF
authors.lastname: Chan
authors.affiliation: State Key Laboratory for Emerging Infectious Diseases, Carol Yu's Centre for Infection and Division of Infectious Diseases.
authors.forename: Can
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, China.
authors.forename: Hou-Shun
authors.initials: HS
authors.lastname: Zhu
authors.affiliation: State Key Laboratory for Emerging Infectious Diseases, Carol Yu's Centre for Infection and Division of Infectious Diseases.
authors.forename: Patrick
authors.initials: P
authors.lastname: Li
authors.affiliation: State Key Laboratory for Emerging Infectious Diseases, Carol Yu's Centre for Infection and Division of Infectious Diseases.
authors.forename: Clara
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, China.
authors.forename: Tuen-Ching
authors.initials: TC
authors.lastname: Chan
authors.affiliation: State Key Laboratory for Emerging Infectious Diseases, Carol Yu's Centre for Infection and Division of Infectious Diseases.
authors.forename: Vincent C C
authors.initials: VC
authors.lastname: Cheng
authors.affiliation: State Key Laboratory for Emerging Infectious Diseases, Carol Yu's Centre for Infection and Division of Infectious Diseases.
authors.forename: Kwok-Hung
authors.initials: KH
authors.lastname: Chan
authors.affiliation: State Key Laboratory for Emerging Infectious Diseases, Carol Yu's Centre for Infection and Division of Infectious Diseases.
authors.forename: Kwok-Yung
authors.initials: KY
authors.lastname: Yuen
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects; D000287:Administration, Topical; D000368:Aged; D000369:Aged, 80 and over; D000634:Aminoquinolines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D000077271:Imiquimod; D009980:Influenza A virus / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D007271:Injections, Intradermal; D008297:Male; D008875:Middle Aged
chemical_list: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D000077271:Imiquimod
keywords: imiquimod; immunogenicity; influenza; intradermal; vaccine