Rabies vaccine response measurement is assay dependent

Abstract

Vaccine equivalency, booster administration, and animal import decisions are based in part on the level of rabies virus neutralizing antibody (RVNA) in serum. Serum neutralization (SN) is commonly used but other methods are employed. Studies have shown that although enzyme-linked immunosorbent assay (ELISA) and SN results are correlated, exact comparison cannot be ensured. This study investigated the applicability of the recognized 0.5 IU/mL cut-off value between methods. Serum from rabies vaccinated subjects grouped by vaccine and vaccination regimen were collected on days 0, 14, 30, and 90 and tested by both SN and ELISA methods. At each time-point, the percentage of subjects producing anti-rabies antibodies above the cut-off as well as the individual results were compared. Similar vaccine equivalency conclusions were made using either method, however vaccination-regimen equivalency varied by test method used. The greatest difference in results between test methods was in samples collected at days 14 and 30. This is the first study comparing SN to ELISA results of samples covering a time-point range, allowing evaluation of rabies antibody response kinetics as defined by test method. SN methods and ELISA methods measure different antibody functions; thus the cut-off values should be independently determined, not extrapolated between different methods.

Keywords: Antibody; ELISA; Rabies; Serum neutralization; Vaccine.