A Double-blind, Randomized Phase 2 Controlled Trial of Intradermal Hepatitis B Vaccination With a Topical Toll-like Receptor 7 Agonist Imiquimod, in Patients on Dialysis

Clin Infect Dis. 2021 Jul 15;73(2):e304-e311. doi: 10.1093/cid/ciaa804.


Background: Patients on dialysis are hyporesponsive to the hepatitis B virus vaccines (HBVv). We examined intradermal (ID) HBVv Sci-B-Vac, with topical Toll-like receptor 7 (TLR7) agonist imiquimod pretreatment in dialysis patients.

Methods: We enrolled and prospectively followed adult patients on dialysis between January 2016 and September 2018. Eligible patients were randomly allocated (1:1:1) into 1 treatment group, topical imiquimod cream followed by ID HBVv (IMQ + ID); and 2 control groups: topical aqueous cream (placebo) followed by ID HBVv (AQ + ID) or topical aqueous cream followed by intramuscular HBVv (AQ + IM). The primary endpoint was the seroprotection rate (hepatitis B surface antibody ≥10 mIU/mL) at 52 weeks.

Results: Ninety-four patients were enrolled, among which 57.4% were previous nonresponders. Seroprotection rate was significantly better at week 52 for the IMQ + ID group with 96.9% compared to 74.2% and 48.4% for AQ + ID and AQ + IM groups, respectively (P < .0001). The geometric mean concentration was significantly higher at week 52 for the IMQ + ID group: 1135 (95% confidence interval [CI], 579.4-2218.2) mIU/mL, compared to 86.9 (95% CI, 18.5-409.3) mIU/mL and 7.2 (2.0-26.5) mIU/mL for the AQ + ID and AQ + IM groups, respectively (P < .0001). IMQ + ID vaccination (odds ratio, 3.70 [95% CI, 1.16-11.81]; P = .027) was the only factor independently associated with higher 52-week seroprotection rate. Adverse reaction was infrequent.

Conclusions: Pretreatment with topical imiquimod before ID HBVv Sci-B-Vac was safe with favorable seroprotection in dialysis patients.

Clinical trials registration: NCT02621112.

Keywords: TLR7 agonist; dialysis; hepatitis B vaccination; intradermal.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Hepatitis B Vaccines
  • Hepatitis B*
  • Humans
  • Imiquimod
  • Injections, Intradermal
  • Injections, Intramuscular
  • Renal Dialysis
  • Toll-Like Receptor 7*
  • Vaccination


  • Hepatitis B Vaccines
  • Toll-Like Receptor 7
  • Imiquimod

Associated data

  • ClinicalTrials.gov/NCT02621112