Background: The existing four-week pre-exposure rabies vaccination schedule is costly and often not practicable. Shorter effective schedules would result in wider acceptance.
Methods: We conducted a non-inferiority trial in 500 healthy adults comparing the safety and immunogenicity of a two-visit (day 0 and day 7) intradermal (ID) primary vaccination (two doses of 0.1 ml ID of the human diploid cell culture rabies vaccine (HDCV) at day 0 and 7) versus a standard three-visit schedule (single dose of 0.1 mL ID at day 0, 7, and 28). One to three years after primary vaccination, a single booster dose of 0.1 mL ID of HDCV was given to evaluate the anamnestic rabies antibody response. The primary endpoint for immunogenicity was the percentage of subjects with an adequate antibody level >0.5 IU/mL seven days after the booster injection. The safety endpoint was the proportion of participants developing adverse reactions following the primary vaccination and/or booster dose.
Results: All subjects in both study groups possessed a rabies antibody titer >0.5 IU/mL on day 7 following the booster dose. Following the booster dose, subjects exposed to the double-dose two-visit ID schedule had a geometric mean titer of 37 IU/ml versus 25 IU/ml for the single-dose three-visit schedule (p<0.001). Local reactions at the injection site following primary vaccination were mild and transient.
Conclusion: In healthy adults, ID administration of a double dose of 0.1 ml of HDCV over two-visits (day 0 and day 7) was safe and not inferior to the single-dose three-visit schedule.