Immunogenicity and effectiveness of post-exposure rabies prophylaxis with a new chromatographically purified Vero-cell rabies vaccine (CPRV): a two-stage randomised clinical trial in the Philippines

Recent improvements in chromatographic purification procedures have made ir possible to develop a new chromatographically purified rabies vaccine (CPR V) by further purifying the current rabies vaccine prepared from Vero-cell culture (PVRV) (Verorab(TM); Pasteur Merieux Connaught). The immunogenicity and effectiveness of post-exposure rabies prophylaxis with this new vaccin e were evaluated in a two-stage clinical trial conducted in the Philippines . In both study stages, post-exposure treatment consisted of five injection s of vaccine [(D)ays 0, 3, 7, 14, 28], together with a dose of rabies immun oglobulin (RIG) of equine or human origin on D0. In stage 1, 231 subjects w ith low-risk rabies exposure (WHO category I or II), and who had a negative ERIG skin test, were treated with either CPRV (n = 114) or PVRV (n = 117). By D14, all subjects in each group had achieved rabies antibody titres ove r ten times that recommended by the WHO as indicating seroconversion (great er than or equal to 0.5 IU/ml). The kinetics of the immune response to vacc ination were very similar in the two groups, and at D28, the immunogenicity of CPRV was equivalent to that of PVRV (one-sided equivalence test). Follo wing these positive results, 132 subjects with severe rabies exposure were included in the second stage of this trial. All were scheduled to receive f our vaccine doses with CPRV. After D14, only those 57 patients with confirm ed rabies exposure (animal with positive FA test) and seven patients for wh om rabies exposure could not be excluded (animal lost or not tested) comple ted the treatment and were followed for one year to assess survival. After 1 year, 62 patients treated for confirmed or possible severe rabies exposur e had been examined and were still alive. Two patients contacted by letter and telephone confirmed good health 7 and 16 months after exposure. No seve re local or systemic reactions were reported in either stage of the study, and no treatment-related serious adverse event occurred. This two-stage cli nical trial attests to the safety and satisfactory immunogenicity of CPRV i n post-exposure rabies treatment, and confirms the effectiveness of a new r abies vaccine in patients with severe confirmed exposure. (C) 2000 Elsevier Science B.V. All rights reserved.