| Description |
A murine model simulating human street rabies virus infection was used to evaluate the post-exposure efficacy of polyinosinic-polycytidylic acid (poly I:C), chlorite-oxidized amylase (COAM), cytosine arabinoside (Ara-C), adenine arabinoside (Ara-A), and 6-azauridine (6-Azu). In addition, this model was used to determine the post-exposure effectiveness of four inactivated rabies vaccines when used alone as well as in combination with poly I:C therapy. The results of these studies indicate that post-exposure treatment with poly I:C significantly reduced mortality in mice challenged with street rabies virus. Successful therapy was associated with the injection (im) of poly I:C into the same site as challenge virus, while in only one instance did protection result from the injection of poly I:C into the opposite limb. Pretreatment of mice with COAM 3 h prior to poly I:C stimulation resulted in an enhancement of the serum interferon response. However, the increased interferon titers were not reflected by increased protection against rabies infection over that achieved with poly I:C therapy alone. In experiments designed to determine the mechanism involved in protection with poly I:C, it was demonstrated that muscle tissue injected with poly I:C contained four to eight times more interferon than comparable muscle tissue taken from the opposite leg of the same animal. Furthermore, exogenous interferon injected into the same site as virus challenge was also effective in reducing rabies mortality; however, the same quantity of interferon injected into the opposite limb was totaling ineffective. Three of the rabies vaccines used in these studies was not efficacious against rabies virus challenge despite the induction of substantial levels of neutralizing antibody. However, treatment with these same vaccines combined with poly I:C therapy resulted in highly significant protection from rabies infection. The level of protection exceeded that achieved with poly I:C therapy alone. The hamster kidney vaccine was effective in reducing rabies mortality over a 25-fold concentration range. However, combined treatment with this vaccine and poly I:C did not result in an increased level of protection. The data further indicate that protection was not directly correlated with the magnitude of the serum neutralizing antibody response. The antiviral agents Ara-C, Ara-A and -Azu were effective in reducing rabies virus replication in vitro. However, treatment of mice challenged with rabies virus with these same drugs was not associated with reduced mortality. It was concluded from these studies that the induction of local interferon combined with an immune response both contribute to the post-exposure protection of mice against street rabies virus infection. The use of poly I:C as an adjunct to active vaccination should be seriously considered in the treatment of exposure to rabies virus. |
