Recent improvements in chromatographic purification procedures have made it possible to develop a new chromatographically purified
rabies vaccine (CPRV) by further purifying the current
rabies vaccine prepared from Vero-cell culture (PVRV) (Verorab;
Pasteur Merieux Connaught). The immunogenicity and effectiveness of post-exposure
rabies prophylaxis with this new
vaccine were evaluated in a two-stage clinical trial conducted in the Philippines. In both study stages. post-exposure treatment consisted of five
injections of
vaccine [(D)ays 0, 3, 7, 14, 28], together with a dose of
rabies immunoglobulin (RIG) of equine or human origin on D0. In stage 1, 231 subjects with 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 over ten times that recommended by the WHO as indicating seroconversion (> or = 0.5 IU/ml). The kinetics of the immune response to vaccination were very similar in the two groups, and at D28, the immunogenicity of CPRV was equivalent to that of PVRV (one-sided equivalence test). Following these positive results, 132 subjects with severe
rabies exposure were included in the second stage of this trial. All were scheduled to receive four
vaccine doses with CPRV. After D14, only those 57 patients with confirmed
rabies exposure (animal with positive FA test) and seven patients for whom
rabies exposure could not be excluded (animal lost or not tested) completed the treatment and were followed for one year to assess survival. After 1 year, 62 patients treated for confirmed or possible severe
rabies exposure had been examined and were still alive. Two patients contacted by letter and telephone confirmed good health 7 and 16 months after exposure. No severe local or systemic reactions were reported in either stage of the study, and no treatment-related serious adverse event occurred. This two-stage clinical trial attests to the safety and satisfactory immunogenicity of CPRV in post-exposure
rabies treatment, and confirms the effectiveness of a new
rabies vaccine in patients with severe confirmed exposure.