Evaluation of the safety, immunogenicity, and pharmacokinetic profile of a new, highly purified, heat-treated equine rabies immunoglobulin, administered either alone or in association with a purified, Vero-cell rabies vaccine

• Published in: Acta tropica 1998-07, Vol.70 (3), p.317-333
• Main Authors: Lang, J., Attanath, P., Quiambao, B., Singhasivanon, V., Chanthavanich, P., Montalban, C., Lutsch, C., Pepin-Covatta, S., Le Mener, V., Miranda, M., Sabchareon, A.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Animals; Antibodies, Viral - blood; Antibodies, Viral - urine; Area Under Curve; Biological and medical sciences; Biological Availability; Cercopithecus aethiops; Double-Blind Method; Equine rabies immunoglobulin; Heat-treated; Horses; Human viral diseases; Humans; Immunoglobulin Fab Fragments - blood; Immunoglobulin Fab Fragments - immunology; Immunoglobulin Fab Fragments - therapeutic use; Immunoradiometric Assay; Infectious diseases; Male; Medical sciences; Middle Aged; Pharmacokinetic; Philippines - epidemiology; Post-exposure treatment; Prospective Studies; Purified; Rabbits; Rabies - drug therapy; Rabies - epidemiology; Rabies - prevention & control; Rabies Vaccines; Rabies virus - immunology; Regression Analysis; Safety; Thailand - epidemiology; Vero Cells; Vero-cell rabies vaccine; Viral diseases; Viral diseases of the nervous system
• ISSN: 0001-706X; 1873-6254
• DOI: 10.1016/S0001-706X(98)00038-2

A clinical evaluation of a new, purified, heat-treated equine rabies immunoglobulin (PHT-Erig), F( ab′) 2 preparation, was carried out in Thailand and in the Philippines—two countries where rabies is endemic. An initial prospective, randomised, controlled trial (Study 1), compared the safety and pharmacokinetics (serum concentrations of rabies antibodies) after administration either of PHT-Erig or of a commercially-available, equine rabies immune globulin (Erig PMC). A second trial (Study 2) simulated post-exposure rabies prophylaxis by using a reference cell culture vaccine, the purified Vero-cell rabies vaccine (PVRV), administered in association with either Erig PMC or PHT-Erig. In Study 1, 27 healthy, Thai adults received a 40 IU kg −1 dose of either Erig PMC ( n=12) or PHT-Erig ( n=15) via the intramuscular (IM) route; half of the dose was injected into the deltoid area and the other half into the buttocks. Serum for rabies antibody determination and F( ab′) 2 concentration was collected at hours (H) 0, 6 and 12, and on day (D) 2, 3, 4, 6, 8, 10, 12 and 15. Both products were safe, with no serious adverse events, and in particular, no anaphylactic reactions or serum sickness was reported. A statistical comparison of the pharmacokinetic parameters did not demonstrate bioequivalence of the two products. Nonetheless, the relative bioavaibility of 93% and the similar absorption rates suggest the pharmacokinetic profiles of Erig and PHT-Erig are similar. The antibody level in either group were low throughout the 15-day study period. The geometric mean titer (GMT) values ranged from group 0.027–0.117 IU ml −1 in the Erig group and from 0.029 to 0.072 IU ml −1 in the PHT-Erig. There was no significant difference between the evolution of GMT values for the two groups. In Study 2, 71 healthy volunteers received 40 IU kg −1 via the intramuscular route of either Erig PMC ( n=36) or PHT-Erig ( n=35) on D0, in association with five doses of PVRV on D0, D3, D7, D14 and D28. The safety evaluation was performed during the 28-day follow-up and serum samples for anti-rabies antibody titration were collected on D0 (before injection) D3, D7, D14 and D28. No serious reactions were reported in either group. In particular, no immediate (anaphylactic type) or delayed (serum sickness) allergic reactions were observed. Over the 28-day follow-up period, GMT profiles of the two groups were statistically equivalent. On D14, 100% of the subjects had protective antibody titers (ant