No abstract

A murine model simulating human street rabies virus infection was used to evaluate the efficacy of polyriboinosinic-polyribocytidylic acid (poly I-poly C), three rabies vaccines, and combinations of these modes of therapy administered after exposure. One or two doses of 100 mug of poly I-poly C, injected into the same intramuscular site as the challenge virus, significantly reduced the mortality rate when therapy was initiated 3 hr after challenge; however, the same quantity of poly I-poly C injected into the opposite leg did not reduce the mortality rate. The muscle injected with poly I-poly C invariably contained four to eight times more interferon than a similar noninjected muscle from the same animal. Mice treated 3 hr after challenge with each of the three vaccines produced significant levels of antibody but were not protected, whereas treatment with combinations of poly I-poly C and vaccine resulted in significant protection. These results suggest that the combination of induction of local interferon and an immune response contributes to the protection of mice after exposure to street rabies virus infection.

Four patients with recurrent staphylococcal furonculosis and deep abscess formation were evaluated to determine if a defect in the host defense mechanism could account for the unusual incidence of infection. Each also suffered repeated allergic rhinitis, often preceding the onset of infection. A marked defect in neutrophil granulocyte chemotaxis occurred when the patients were symptomatic with rhinitis and abscess formation. Their mean chemotactic index (+/- SD) was 16 +/- 6, while that of 25 control subjects was 70 +/- 11. Neutrophil random migration, phagocytosis, bactericidal activity, and lymphocyte T-cell populations were normal, as were serum concentrations of IgA, IgG, IgM, and IgE. Serial neutrophil function tests revealed normal chemotactic responsiveness when the patients were symptom-free of allergic rhinitis and no longer having abscesses. Abnormal function returned, however, when symptoms recurred. These studies suggest that defective neutrophil function associated with allergic phenomena need not be accompanied by hyperimmunoglobulinemia E. Such defects may be intermittent, appearing when allergic symptomatology and infections develop.

The antiviral agents cytosine arabinoside, adenine arabinoside, and 6-azauridine were shown to inhibit the replication of rabies virus in vitro but not the replication of Sindbis virus. These same drugs were not effective in reducing the mortality rate in mice challenged with street rabies virus.

Chlorite-oxidized amylose (COAM), polyinosinic-polycytidylic acid [poly(I:C)], and combinations of the two drugs were evaluated for their interferon-inducing properties and their ability to protect mice against rabies infection. Post-exposure administration of one or two doses (100 μg each) of poly(I:C) significantly protected mice against rabies infection. Pretreatment of mice with COAM 3 h before poly(I:C) stimulation resulted in an enhancement of the 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. Therapy with COAM alone did not protect mice against rabies but, rather, was associated with enhanced mortality.