Evaluation of a new five-injection, two-site,intradermal schedule for purified chick embryo cell rabies vaccine: A randomized, open-label, active-controlled trial in healthy adult volunteers in India.

BACKGROUND

Human rabies is an ongoing significant public health problem inmany developing countries, with India reporting the highest incidence of rabies-related deaths (∼20,000 per year). Many people living in India cannot afford the standard IM postexposure prophylaxis (PEP) with cell-culture vaccines, which are administered using a 5-dose regimen developed in Essen, Germany. A potentially less expensive intradermal (ID) regimen, based on the Essen regimen, has been developed at the Kempegowda Institute of Medical Sciences (KIMS), Bangalore, India.

OBJECTIVE

The objective of this study was to compare the immunogenicity and local and systemic tolerability of the KIMS-1D regimen with those of the standard Essen IM regimen in healthy adult volunteers in India.

METHODS

This randomized, open-label, active-controlled trial was conductedat the Antirabies Clinic, Medical College, KIMS. Healthy adult volunteers were randomly assigned to receive purified chick embryo cell vaccine (PCECV) using the KIMS-1D regimen (0.1 mL injected ID at 2 body sites on days 0, 3, 7, 14, and 28 ["2-2-2-2-2"]) or the Essen IM regimen (1 mL injected IM at 1 body site on the same days Subjects were followed up for 365 days by the treating physician and encouraged to voluntarily report any adverse events (AEs). Serum rabies virus-neutralizing antibody (RVNA) concentrations were measured before the first injection on day 0 (baseline) and on days 14, 28, 90, 180, and 365, using the rapid fluorescent focus inhibition test.

RESULTS

Ninety-one subjects were enrolled and included in the tolerabilityand immunogenicity analyses. The ID group comprised 45 subjects (26 men, 19 women; mean [SD] age, 20.84 [1.48] years); the IM group, 46 subjects (28 men, 18 women; mean [SD] age, 21.02 [1.16] years). The most common local AEs were pain at the injection site (2/225 [0.9%] in the ID group and 10/230 [4.3%] in the IM group; P < 0.006) and itching at the injection site (5/225 [2.2%] in the ID group and none in the IM group; P = 0.026). All of the AEs were transient and resolved without the need for medication. All subjects had serum RVNA concentrations ≥0.5 IU/mL-considered protective by the World Health Organization-at all follow-up visits. However, the mean RVNA concentrations in the IM group were significantly higher compared with those in the ID group from days 14 to 365 (all, P < 0.001).

CONCLUSION

In this study in healthy volunteers, PEP with PCECV administered using the KIMS-ID regimen was well tolerated and immunologically efficacious for 365 days. Adequate RVNA levels were maintained with the KIMS-ID regimen from days 14 to 365, although these levels were significantly lower than those achieved in the group receiving the Essen IM regimen (all, P < 0.001).