Rabies: Pre- and post-exposure studies with human diploid cell strain vaccine.

This thesis studies the efficacy of human diploid cell strain rabies vaccine (HDCSV) in man. After a definition of rabies and a historical introduction a searching critical review is presented of all published work on the epidemiology of rabies, the virus, its replication, transmission and the pathogenesis; of human rabies, its pre-and postexposure prophylaxis; the adverse effects of treatment, and an assessment of immunity. The review reveals a desperate need for improved methods of treatment, setting the scene in 1975 when the studies began. Following a description of the volunteers, materials and methods is an account of rabies virus interference and the interference inhibition test which was developed as an alternative to the mouse neutralisation test (MNT). Restrictions in the use of rabies virus led to the rabies enzyme-linked immunosorbent assay (ELISA) described and used in later studies. Studies 1,2, 9 and 11 show that HDCSV is well tolerated by the intramuscular and intradermal routes and that both reliably induce high antibody titres, irrespective of age, sex, vaccine batch, ambient temperature, and passive immunisation. Studies 3 - 6 show that primary immunisation, not boosters, generally induces circulating interferon and that the interferon and humoral responses are poorly correlated. Studies 7 and 8 reveal a T-cell-mediated blast-transformation response in most vaccinees. Studies 9 and 10 show that satisfactory seroconversion rates are possible in busy centres using the intradermal route and that once only, postexposure, intradermal administration of 4 X 0.2ml HDCSV protects rabbits from street rabies virus. Studies 12-14 evaluate abbreviated candidate schedules of immunisation in Thais, one - a multisite intradermal schedule - was given to 78 patients bitten by rabid animals. A further 77 patients were treated with Semple vaccine. All patients survived. In conclusion, HDCSV is considered safe, thermostable and antigenic, and the intradermal route provides effective economical alternatives to the intramuscular route for both pre- and postexposure prophylaxis.