In healthy adults, intradermal (ID) administration of a double dose of 0.1 mL (0.1ID) of human diploid cell culture rabies vaccine (HDCV) over the course of 2 visits (day 0 and day 7) was safe and not inferior to the single-dose 3-visit ID schedule, according to a study recently published in Clinical Infectious Diseases.
Rabies is an often overlooked tropical disease with a case fatality of nearly 100%. Pre-exposure prophylaxis (PrEP) using rabies vaccine is an important cornerstone in rabies prevention. Because the previous 4-week PrEP schedule was often not practicable, an effective and safe double-dose 2-visit ID and single-dose 2-visit intramuscular (IM) schedule has been recommended as a first-line regimen by the World Health Organization, with the primary aim of wider acceptance and use in international travelers and in subjects at risk in endemic countries, especially children.
Administration of 0.1 mL ID has proven to be as immunogenic as the 1.0-mL IM dose vaccination and also offers substantial cost savings. In addition, ID injections induce a more rapid immune response compared with IM injections. Therefore, this noncommercial non-inferiority trial aimed to compare immunogenicity 7 days after a single ID booster injection following 2 different primary schedules 1 to 3 years earlier: a double-dose 2-visit (2ID; days 0 and 7) rabies ID vaccination schedule vs a single-dose 3-visit schedule (3ID; days 0, 7, and 28).
The primary objective was to demonstrate non-inferiority of the 2-visit ID schedule compared with the established 3-visit ID schedule, as assessed by the proportion of participants with adequate rabies antibody titers, measured by rapid fluorescent focus inhibition test, above 0.5 IU/mL 7 days after a booster vaccine injection, which was administered 1 to 3 years after primary vaccination. Clinical non-inferiority was defined as a loss of no more than 10% of participants who have adequate rabies antibody levels compared with the 3-visit ID schedule. A total of 500 participants were included and randomly assigned. Moreover, among the participants completing the primary vaccination schedules in the 3-visit ID (n=240) and 2-visit ID (n=242) schedules, 83% and 87% received the booster injection, respectively.
Non-inferiority was met for the primary immunogenicity endpoint, with 100% observed adequate antibody response (>0.5 IU/mL) observed 7 days after booster dose injection of 0.1 mL ID. Furthermore, analysis of secondary endpoints highlighted the superiority of the 2-visit ID schedule following booster injection, both in the proportion of participants with long-lasting protection >10 IU/mL (96% vs 83%) and for the obtained geometric mean titer (GMT). Subjects exposed to the 2-visit ID schedule had a GMT of 37 IU/mL vs 25 IU/mL for the 3-visit ID schedule (P <.001). All subjects in the per-protocol and intention-to-treat analysis sets attained rapid fluorescent focus inhibition test results of >0.5 IU/mL at day 35 following primary vaccination. The number of subjects with systemic discomfort related to injections was very low and did not differ significantly between the 2 groups following primary vaccination (P =.42) or booster injection (P =1).
Overall, the study authors conclude that, “Safe and effective PrEP for travelers or people living in endemic rabies regions may be achieved with a double-dose two-visit 0.1ID regimen, with 100% adequate antibody response following a booster injection of 0.1ID 1 to 3 years after primary vaccination.”
Soentjens P, Andries P, Aerssens A, et al. Pre-exposure intradermal rabies vaccination: a non-inferiority trial in healthy adults on shortening the vaccination schedule from 28 to 7 days [published online June 25, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy513/5043520.