Intranasal Infection of Monkeys with Japanese Encephalitis Virus: Clinical Response and Treatment with a Nuclease-Resistant Derivative of Poly(I)·Poly(C) *

Harrington, D. G.; Hilmas, Duane E.; Elwell, Michael R.; Whitmire, Richard E.; Stephen, Edward L.

doi:10.4269/ajtmh.1977.26.1191

Cited by 47 publications

(24 citation statements)

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“…The critical relationships in prophylaxis or treatment between dose of dsRNA and effective dose of virus have been emphasized by Stephen et al (1977) and Levy et al (1976) in their tests in rhesus monkeys infected by the viruses of simian haemorrhagic fever or yellow fever: their results suggest that dsRNA impaired infection and replication but did not modify the course of disease in those still infected by minimal doses of virus. Similar conclusions emerge from the studies by Harrington et al (1977) on the treatment with poly(I), poly(C) of rhesus monkeys infected with Japanese encephalitis virus. The studies by Bowen et al (1978) on Ebola virus infections in interferon-treated rhesus monkeys showed a delay in viraemia without change in the ultimate course or severity of disease.…”

Section: Discussionsupporting

confidence: 73%

The Effects of Interferon and Double-stranded RNA upon the Virus-Host Interaction: Studies with Togavirus Strains in Mice

Bradish¹,

Titmuss

1981

Journal of General Virology

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Section: Discussionsupporting

confidence: 73%

The Effects of Interferon and Double-stranded RNA upon the Virus-Host Interaction: Studies with Togavirus Strains in Mice

Bradish¹,

Titmuss

1981

Journal of General Virology

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“…19 In naive monkeys given an intranasal challenge of JEV, 19,20 the response was between that of a peripheral subcutaneous or intradermal challenge, in which monkeys generally do not become ill, and a direct CNS injection, in which paralysis sets in early. Pathology was limited to the nervous system and was similar in all animals.…”

Section: Discussionmentioning

confidence: 99%

Production of lethal infection that resembles fatal human disease by intranasal inoculation of macaques with Japanese encephalitis virus.

Myint

Raengsakulrach²,

Young³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. Twelve rhesus macaques (Macaca mulatta) challenged intranasally with a wild-type Japanese encephalitis virus (JEV) developed clinical signs 11-14 days later. Tissues from the cerebral cortex, cerebellum, brainstem, thalamus, meninges, and all levels of the spinal cord were stained for JEV antigen with hyperimmune mouse ascitic fluid and streptavidin-alkaline phosphatase; immunofluorescent staining was also done on frozen sections. Viral antigen was found in all cell layers of the cerebellum, the gray matter of the thalamus and brainstem, and the ventral horn of all levels of the spinal cord. Staining was limited to neurons and their processes. Histopathologic changes were limited to the nervous system and characterized by nonsuppurative meningoencephalitis. These results were comparable with those of previous studies done with human autopsy tissues. Intranasal inoculation of rhesus monkeys with JEV was effective in producing clinical disease comparable with natural disease in humans and may serve as a model to evaluate protective efficacy of candidate JEV vaccines.Japanese encephalitis (JE), which is endemic to much of eastern and Southeast Asia, is the most common arthropodborne human encephalitis in the world, accounting for more than 35,000 cases and 10,000 deaths each year. 1 In endemic areas, the highest age-specific attack rates occur in children 3-6 years of age. Infection with JE virus (JEV) may be asymptomatic or manifest as a mild febrile illness, aseptic meningitis, or classic severe meningomyeloencephalitis. The case fatality rate is approximately 25%, with 50% having neuropsychiatric sequelae and 25% recovering fully. 2,3 Longterm sequelae in survivors include weakness, ataxia, tremors, athetoid movements, paralysis, memory loss, and abnormal emotional behavior. 4,5 The principle vector for JEV in Thailand is the mosquito Culex tritaeniorhynchus, which is difficult to control.The current highly purified BIKEN (Research Foundation of Microbial Diseases

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“…This challenge model has been used previously to demonstrate the protective efficacy of an inactivated vaccine 30 and of interferon inducers against JE. 16,31 Compared with the previous studies, ours provides a more extensive characterization of the model. Because the challenge virus was carefully titered in monkeys, a high level of reproducibility of this model is likely.…”

Section: Discussionmentioning

confidence: 99%

“…This disease progression was similar to that seen in a previous study. 16 In that study, the onset occurred on days 5-9 and death ensued 11-12 days after intranasal inoculation. One striking difference between that study and ours is that the ED 50 of JEV (Peking strain) used in that study was 2.5 ϫ 10 4 pfu, which is 2,400 times lower than the ED 50 of 6.0 ϫ 10 7 pfu of our Thai strain.…”

Section: Discussionmentioning

confidence: 99%

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An intranasal challenge model for testing Japanese encephalitis vaccines in rhesus monkeys.

Raengsakulrach¹,

Nisalak²,

Gettayacamin³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. Placebo-controlled field efficacy trials of new Japanese encephalitis (JE) vaccines may be impractical. Therefore, an animal model to evaluate efficacy of candidate JE vaccines is sought. Previous work has shown that exposure of monkeys to JE virus (JEV) via the intranasal route results in encephalitis. Here we report the further development of this model and the availability of titered virus stocks to assess the protective efficacy of JE vaccines. To determine the effective dose of our JE challenge virus, dilutions of a stock JEV (KE-93 isolate) were inoculated into four groups of three rhesus monkeys. A dose-dependent response was observed and the 50% effective dose (ED 50 ) was determined to be 6.0 ϫ 10 7 plaque forming units (pfu). Among animals that developed encephalitis, clinical signs occurred 9-14 days postinoculation. Infection with JEV was confirmed by detection of JEV in nervous tissues and IgM to JEV in the cerebrospinal fluid. Viremia with JEV was also detected intermittently throughout infection. Validation of the model was performed using a known effective JE vaccine and saline control. One ED 90 of virus (2.0 ϫ 10 9 pfu) was used as a challenge dose. Four of four animals that received saline control developed encephalitis while one of four monkeys administered the JE vaccine did so. This study demonstrates that the virus strain, route of inoculation, dose, and the outcome measure (encephalitis) are suitable for assessment of protective efficacy of candidate JE vaccines.Japanese encephalitis (JE) is the leading cause of mosquito-borne viral encephalitis in the world, accounting for approximately 35,000 cases and 10,000 deaths each year in Asia. The JE virus (JEV) is transmitted by culicine mosquitoes through an epizootic cycle involving primarily pigs and birds. Most infections in humans are asymptomatic. It is estimated that only one in 20 to one in 1,000 infections result in encephalitis. However, once encephalitis occurs, it is fatal in 25% of the cases with 50% of the survivors experiencing neurologic sequelae. [1][2][3] Several JE vaccines are in use. Live attenuated vaccines have been developed and licensed for use only in China. [4][5][6] A more widely used vaccine is a highly purified formalininactivated virus preparation derived from infected mouse brain. In 1984In -1985, an efficacy trial was conducted in 65,224 Thai children using monovalent (Nakayama strain) and bivalent (Nakayama and Beijing strain) mouse brain vaccines manufactured by BIKEN (Research Foundation of

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Intranasal Infection of Monkeys with Japanese Encephalitis Virus: Clinical Response and Treatment with a Nuclease-Resistant Derivative of Poly(I)·Poly(C) *

Cited by 47 publications

References 0 publications

The Effects of Interferon and Double-stranded RNA upon the Virus-Host Interaction: Studies with Togavirus Strains in Mice

The Effects of Interferon and Double-stranded RNA upon the Virus-Host Interaction: Studies with Togavirus Strains in Mice

Production of lethal infection that resembles fatal human disease by intranasal inoculation of macaques with Japanese encephalitis virus.

An intranasal challenge model for testing Japanese encephalitis vaccines in rhesus monkeys.

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