Pre-exposure intradermal rabies vaccination: a non-inferiority trial in healthy adults on shortening the vaccination schedule from 28 to 7 days

Background: The existing 4-week preexposure rabies vaccination schedule is costly and often not practicable. Shorter effective schedules would result in wider acceptance.

Methods: We conducted a noninferiority trial in 500 healthy adults comparing the safety and immunogenicity of a 2-visit (days 0 and 7) intradermal (ID) primary vaccination (2 doses of 0.1 mL ID of the human diploid cell culture rabies vaccine [HDCV] at days 0 and 7) vs a standard 3-visit schedule (single dose of 0.1 mL ID at days 0, 7, and 28). One year to 3 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 7 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 2-visit ID schedule had a geometric mean titer of 37 IU/mL, compared with 25 IU/mL for the single-dose 3-visit schedule (P < .001). Local reactions at the injection site following primary vaccination were mild and transient.

Conclusions: In healthy adults, ID administration of a double dose of 0.1 mL of HDCV over 2 visits (days 0 and 7) was safe and not inferior to the single-dose 3-visit schedule.

Clinical Trials Registration: NCT01388985, EudraCT 2011-001612-62.