Effect of Administered Interferon on Rabies in Rabbits

Postic, Boško; Fenje, P

doi:10.1128/aem.22.3.428-431.1971

Cited by 24 publications

(14 citation statements)

References 10 publications

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“…However, exogenous interferon similarly administered, but in combination with one dose of vaccine, reduced the mortality. These observations are comparable with those of some other investigators (1)(2)(3)12) and again suggest the importance of interferon or a high level of interferon induction by vaccine in the initial stages of protection against rabies. However, the possibility that the protective activity of interferon is dependent on its activity in regulating cellular immune responses and not on its direct viral inhibition activity, as suggested from the combined effect of interferon and vaccine, should be further investigated.…”

Section: Discussionsupporting

confidence: 91%

A Mouse Model for the Pathogenesis and Postexposure Prophylaxis of Rabies

Mifune

Shichijo

Makino

et al. 1980

Microbiology and Immunology

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A mouse model for the study of postexposure prophylaxis of rabies was established. Mice injected intramuscularly with a street strain of rabies virus were significantly protected from death by five daily 0.2-ml doses of inactivated rabies vaccine of chick embryo cell culture origin initiated immediately or 3 hr after infection. In these mice, a large amount of circulating interferon was induced as early as 1 hr after the first dose of vaccine and lasted until at least 12 hr but no such amount of interferon was induced by additional doses of vaccine.Serum antibody was first detected in the mice on day 6. It was noted that some of the surviving mice manifested an ataxia or paralysis of the legs. Increasing mortality rates were shown in mice treated with decreasing doses of the vaccine.Passive protection tests using concentrated IgG and IgM antibodies with equivalent neutralization titers showed that IgG antibody gave total protection when given 24 hr before the infection, while it was almost totally ineffective in reducing the mortality when given 2 days or more after infection.IgM antibody did not protect the mice even when given 24 hr before infection.These results suggest that interferon production is more important than antibody production in the initial stages of protection by postexposure vaccination.However, the mechanisms of postexposure prophylaxis in this model could not be explained only by the interferon produced by the vaccine and the possible contributions of additional mechanisms were suggested.Recent studies with experimental animals have shown that postexposure administration antibody or exogenous interferon in combination with rabies vaccine (1-3) or endogenous interferon induced by rabies vaccine (1, 24) or by polyriboinosinic-polyribocytidylic acid (5, 6, 8) can be highly effective in the prophylaxis of rabies. In most of those studies, the prophylaxis did not depend on the amount of antirabies neutralizing antibody induced by the vaccine. However, the detailed role of antibody or interferon which is administered or induced by vaccine still remains unclear. A recent report states that hyperimmune antiserum passively transferred after infection with virus did not reduce the mortality but merely 1* Present address:

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Section: Discussionsupporting

confidence: 91%

A Mouse Model for the Pathogenesis and Postexposure Prophylaxis of Rabies

Mifune

Shichijo

Makino

et al. 1980

Microbiology and Immunology

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“…It is known that in rabbits, interferon given intramuscularly or intravenously, or induced by complexed polyriboinosinic polyribocytidylic acid (poly [ ] * poly [C ]), around the time of rabies infection, or even shortly thereafter, may protect the animal from death and paralysis (6,7,12,17). Thus, 8 x 105 U of interferon divided between two intramuscular doses and one intravenous dose, injected 24 h before or up to 3 h after infection, resulted in complete protection (17). Similarly, 1 mg of poly(I) -poly(C) administered intravenously either 24 h before or 3 h after infection with 25 mean lethal dose (LD50) rabies street virus protected rabbits completely (6).…”

mentioning

confidence: 99%

“…Although the above studies are promising as extrapolated to man, they are restrictive because: (i) poly(I) poly(C) is a toxic substance, and its interferon-inducing capacity in man is limited (20); and (ii) regarding exogenous interferon, the best extrapolation from the cited reports is that a presently prohibitive amount of interferon, or at least 70 million units, is needed for one treatment in an adult male exposed to rabies. Also, there appears to be a very short time period after exposure during which treatment is effective (17). It would be highly desirable if a better agent or another method of administration could prolong this time period.…”

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confidence: 99%

Interferon Administered in the Cerebrospinal Space and Its Effect on Rabies in Rabbits

Nash

Morgan

et al. 1974

Infect Immun

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Because combined administration of intramuscular and intravenous interferon has been partially successful in the incubationary treatment of rabies, the effect of direct interferon administration into the cerebrospinal fluid space was tested. After injecting 1,800 U of interferon into the cisterna magna or the lateral ventricle, periodic samples, obtained by cisternal taps, showed that 1 to 5% remained after 24 h, as opposed to the known clearance of interferon from the bloodstream to this level within minutes. The distributions of interferon and 13"I-labeled albumin were similar as demonstrated by kinetics of clearance monitored over 24 h. Beginning with and after experimental infection of rabbits, daily intraventricular injections of one million units of interferon were given for as long as 3 weeks. Interferon was prepared from cell culture fluids after pressure dialysis and chromatography on Sephadex G-100. This intensive treatment did not prevent encephalitis, but prolonged the length of the incubation period by one-to two-thirds. The outcome after intraventricular administration was not as favorable as when one million units equally divided between intramuscular and intravenous injections were given at the time of challenge. Interferon administered in the subarachnoid space in this fashion is apparently inadequate to protect the rabbit against rabies. Its role as an adjunct measure, or other methods of administration in the nervous system, remains to be examined.

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“…Treatment with exogenous IFN was rapidly shown to prevent the replication of RABV in cell cultures [172][173][174][175]. This antiviral property was not related to a virucidal effect [176].…”

Section: Interferons and Interferon-inducing Moleculesmentioning

confidence: 99%

“…Treatment with exogenous homologous or heterologous IFN [175,[183][184][185][186] or inducers of IFN, such as polyriboinosinic-polyribocytidylic acid (poly I:C) [187][188][189], its derivatives containing kanamycin and CaCl 2 (PICKCa) [190] or other structural molecules [191] weaker protection, although the incubation period was prolonged in some treated animals [176,183]. Combinations of drugs, including combinations of IFN-inducers, such as poly I:C, and chlorite-oxidized amylose (COAM), a small inducer of interferon [192], or combinations of rabies vaccines and IFN or IFN inducers [193][194][195] were also effective only when administered close to the time of viral challenge, and the protective effects obtained were variable.…”

Section: Interferons and Interferon-inducing Moleculesmentioning

confidence: 99%

Human Rabies Encephalitis Prevention and Treatment: Progress Since Pasteurs Discovery

Dacheux¹,

Delmas²,

Bourhy

2011

IDDT

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Rabies remains one of the most ancient and deadly of human infectious diseases. This viral zoonosis is transmitted principally by the saliva of infected dogs, inducing a form of encephalomyelitis that is almost invariably fatal. Since the first implementation, by Louis Pasteur in 1885, of an efficient preventive post-exposure treatment, more effective protocols and safer products have been developed, providing almost 100% protection if administered early enough. However, this disease still represents a major, but neglected public health problem, with an estimated 55,000 human deaths due to rabies reported each year, mostly in Africa and Asia. Once the first clinical signs appear, there is no effective treatment. A ray of hope emerged in 2004, with the report of a patient recovering from rabies after aggressive, innovative treatment. However, this case was not clearly reproduced and the identification of targets for antiviral treatment in cases of rabies infection remains a major challenge. In this context, this review presents the state-of-the art in the prevention and curative treatment of human rabies. We begin by describing the viral etiological agent and the disease it causes, to provide an essential background to rabies. An overview of the post-exposure prophylaxis of rabies in humans is then given, from its initial implementation to possible future developments. Finally, an analysis of the various antiviral compounds tested in rabies in vitro, in animal models or in humans is presented, focusing in particular on potential new strategies.

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Effect of Administered Interferon on Rabies in Rabbits

Cited by 24 publications

References 10 publications

A Mouse Model for the Pathogenesis and Postexposure Prophylaxis of Rabies

A Mouse Model for the Pathogenesis and Postexposure Prophylaxis of Rabies

Interferon Administered in the Cerebrospinal Space and Its Effect on Rabies in Rabbits

Human Rabies Encephalitis Prevention and Treatment: Progress Since Pasteurs Discovery

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