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Immunogenicity and protective efficacy of the current inactivated Japanese encephalitis vaccine against different Japanese encephalitis virus strains.

Mouse brain-derived, inactivated Japanese encephalitis (JE) vaccine has been internationally used for many years. It is believed that this vaccine made a great contribution to the reduction of JE patients in several countries. Mouse brain-derived, Beijing-1 and Nakayama JE vaccines induce high levels of neutralizing antibodies. High levels of induced antibodies are maintained at least for 3-4 yr. The induced antibodies are cross-reactive to heterologous strains; however, the neutralizing antibody titers against heterologous strains are usually lower than those against homologous strains. Considering that both Nakayama and Beijing-1 JE vaccines showed high levels of protective efficacy in Taiwan and Thailand where strains other than Nakayama and Beijing-1 were circulating, we conclude that the current inactivated JE vaccine can induce high levels of protective immunity against heterologous JE virus strains.

Animals↗

Epidemiological and ecological studies of Japanese encephalitis in Okinawa, subtropical area in Japan. I. Investigations on antibody levels to Japanese encephalitis virus in swine sera and vector mosquito in Okinawa, Miyako and Ishigaki islands.

From 1985 to 1989, serum specimens of swine raised in the northern, central and southern areas in Okinawa island were examined for Japanese encephalitis (JE) virus antibody by ELISA and hemagglutination-inhibition test. The antibody positive rate was found to be higher in the north and central than in the south. The 2-mercaptoethanol sensitive antibody to JE was detected mostly in June and July, and occasionally in other months except February and March. There was no month when all specimens from three areas turned antibody-negative simultaneously, indicating that JE virus transmission to swine lasted longer in Okinawa island than in other temperature areas in Japan. From 1986 to 1991, the vector mosquitoes (Culex tritaeniorhynchus) were collected in a pig farm in the south of Okinawa island. A total of 153 strains of JE virus was isolated from the vector mosquitoes mainly in June. In Miyako and Ishigaki islands, the antibody positive rate in swine sera was found to be extremely low, compared with that in Okinawa island. In Miyako island, where no paddy rice field is cultivated, a few adults as well as larvae of the vector mosquito were collected, while in Ishigaki island, where there are many watered rice fields, a lot of adults as well as larvae were collected. Although the environmental situation is quite different between the two islands, JE virus transmission appeared to be very low in both islands.

Animals↗

Epidemiological and ecological studies of Japanese encephalitis in Okinawa, subtropical area in Japan. II. Prevalence of Japanese encephalitis antibody in residents in Okinawa, Miyako and Ishigaki islands.

During 1989 to 1990, human sera were collected by age groups in Okinawa (the northern, central and southern areas), Miyako and Ishigaki islands and examined for the neutralization (N) antibodies to two strains, Nakayama (vaccine strain) and C307 (Okinawan strain), of Japanese encephalitis (JE) virus. In Okinawa island, the N antibody positive rate to C307 was higher than that to Nakayama, while in Miyako and Ishigaki islands, the positive rate to Nakayama was higher than that to C307, suggesting that JE virus transmission rate was higher in Okinawa than in Miyako and Ishigaki islands. In Okinawa Prefecture, JE vaccine had not been administered to most of residents over 31 years of age at the time of serum collection. In residents over 31 years old, the positive rate to C307 was highest in the north of Okinawa (83.3%) and was lowest in Miyako (26.3%), with the second lowest in Ishigaki (33.3%). The distribution of N antibody titers to C307 gave hyperbolic patterns in the 0-5 age groups in Miyako and Ishigaki, and also in the 31-40, 41-50 age groups in Miyako and the 41-50 age group in Ishigaki, suggesting low rates of natural infection in these 4-5 decades in both islands. In residents of ages subjected to JE vaccine, a characteristic pattern was obtained, in which the curves to Nakayama shifted to higher titers than those to C307, suggesting that the first antigenic stimulation was caused by vaccine, not by natural infection of JE virus.

Adolescent↗

Induction of protective immunity against Japanese encephalitis in mice by immunization with a plasmid encoding Japanese encephalitis virus premembrane and envelope genes.

A DNA vaccine plasmid containing the Japanese encephalitis (JE) virus premembrane (prM) and envelope (E) genes (designated pcDNA3JEME) was evaluated for immunogenicity and protective efficacy in mice. Two immunizations of 4-week-old female ICR mice with pcDNA3JEME by intramuscular or intradermal injections at a dose of 10 or 100 microg per mouse elicited neutralizing (NEUT) antibodies at titers of 1:10 to 1:20 (90% plaque reduction), and all immunized mice survived a challenge with 10,000 50% lethal doses of the P3 strain of JE virus. A single immunization with 100 microg of pcDNA3JEME did not elicit detectable NEUT antibodies but induced protective immunity. Spleen cells obtained from BALB/c mice immunized once with 10 or 100 microg of pcDNA3JEME contained JE virus-specific memory cytotoxic T lymphocytes (CTLs). BALB/c mice maintained detectable levels of memory B cells and CTLs for at least 6 months after one immunization with pcDNA3JEME at a dose of 100 microg. The CTLs induced in BALB/c mice immunized twice with 100 microg of pcDNA3JEME were CD8 positive and recognized mainly the envelope protein. These results indicate that pcDNA3JEME has the ability to induce a protective immune response which includes JE virus-specific antibodies and CTLs.

Animals↗

Vector competence of California mosquitoes for California encephalitis and California encephalitis-like viruses.

Mosquitoes collected from coastal, inland valley, and alpine locations in California were evaluated for their experimental vector competence for two viruses in the California serogroup (Bunyaviridae:Bunyavirus). Aedes squamiger, a coastal salt marsh mosquito, was an efficient vector of a California encephalitis (CE)-like virus isolated from its habitat (89% of the pledget-fed females became infected and 61% transmitted virus). Aedes dorsalis, a coastal mosquito, and Ae. melanimon, an inland valley mosquito, were competent vectors of prototype CE virus (98% and 100% of the pledget-fed females became infected and 56% and 30%, respectively, transmitted virus). Aedes squamiger and Ae. dorsalis transmitted both viruses vertically to one or more of 20 of their progeny. Culiseta inornata was susceptible to infection with both viruses, but 5% or less transmitted virus perorally. Alpine mosquitoes, Ae. cataphylla, Ae. increpitus, and Ae. tahoensis, became infected with both CE and CE-like viruses, but 3% or less transmitted virus. All species of mosquitoes were more efficient vectors of both viruses following intrathoracic inoculation than following pledget feeding, suggesting the presence of mesenteronal barriers.

Animals↗

Subpopulation of peripheral blood lymphocytes in human encephalitis caused by group B arboviruses (Dengue, West Nile and Japanese B encephalitis.

Sera from twenty patients with clinically diagnosed viral encephalitis were studied during the acute and convalescent phases of illness for evidence of group B arboviral infection by demonstrating a rise in the titre of haemagglutination inhibiting (HI) antibodies. The immune status of these individuals was studied by quantitating peripheral T, T and 'null' lymphocytes. The percentage of total T cells in arboviral encephalitic (AE) group decreased significantly while that of B cells and 'active' T cells remained unaltered when compared to that of normal individuals. The null cell percentage, on the other hand increased significantly in the AE group. The absolute number of circulating T and B cells did not alter in the AE group while that of null cells rose significantly. The percentage and concentration of T. B and null cells during the convalescent phase of AE did not differ significantly when compared to those of the acute phase.

Acute Disease↗

Studies on Japanese encephalitis virus infection of reptiles. II. Role of lizards on hibernation of Japanese encephalitis virus.

A series of experiments on the role of lizards as overwintering hosts of Japanese encephalitis virus (JEV) was carried out. Two species of lizards, T. tachydromoides and E. latiscutatus, 2 species of mosquitoes, Cx. p. fatigans and Cx. p. pallens, and 2 strains of JEV, JaGAr#01 and JaGAr 19461, were used in this study. Firstly transmission of JEV from infected mosquitoes to uninfected lizards and from infected lizards to normal mice by the bite of mosquitoes was demonstrated successfully. Cx. pipiens group mosquitoes were found to feed readily on lizards as compared to Cx. tritaeniorhynchus, the primary vector of JEV in Japan. Secondly simulated hibernation of JEV in lizards was carried out under indoor and outdoor conditions. In the outdoor hibernation, lizards were injected with JEV on October 14, 1968, entered in hibernation on October 19 and were recovered from hibernation on April 10, 1969. Viremias were demonstrated in the lizards for a few weeks in late April. Thirdly JEV isolation and HI antibody detection were attempted from blood samples of field-caught reptiles, 7 species of snakes and 3 species of lizards and among amphibians, 2 species of frogs. HI antibody against JEV was found at a rate of 14.3% from E. latiscutatus and 4.0% from T. tachydromoides, though JEV was not isolated from all the blood samples of these cold-blooded animals. The roles of lizards as overwintering hosts of JEV were discussed.

Animals↗

[Use of inbred mice for assessing the neurovirulence of strains of the tick-borne encephalitis virus complex and the immunogenicity of a concentrated tick-borne encephalitis vaccine].

The sensitivity of different lines of inbred mice to strains of the tick-borne encephalitis complex viruses differing in their biological properties and the degree of attenuation was compared. The mice differing in their genetic characteristics and susceptibility to extraneurally inoculated virus were shown to have different immunological responsiveness to inoculation of an inactivated vaccine antigen.

Animals↗

The isolation of Central European encephalitis (tick-borne encephalitis) virus from Ixodes ricinus (L.) ticks in southern-Germany.

During the years 1972--1976 a total of 14.692 ticks of the species Ixodes ricinus (L.), (2.738 adults and 11.954 nymphs) was collected. They were taken from five areas where human Central European encephalitis virus (CEE) infections had occurred. By means of, intracerebral (IC) and subcutaneous (SC) isolation experiments with suckling mice 19 agents, exhibiting the pathogenic characteristics of CEE virus, were isolated from these ticks. In neutralization tests with suckling mice these isolates could be identified as CEE virus strains. From the 14.692 ticks at least 1.29% were virus carriers as evidenced by the number of isolated virus strains. By the same reasoning at least 3.6% of the adults and 0.76% of the nymphs must have contained virus. We were successful in each of the five areas, rather distant from each other, to isolate the virus. The favorable ecological conditions for the main vector Ixodes ricinus in the Federal Republic of Germany give rise to the assumption that this medically important tick-borne disease might be permanently present in many areas.

Animals↗

Immune response to caprine arthritis-encephalitis virus surface protein induced by coimmunization with recombinant vaccinia viruses expressing the caprine arthritis-encephalitis virus envelope gene and caprine interleukin-12.

The objective of this study was to determine if interleukin (IL)-12 can focus an antigen specific type 1 immune response characterized by activation of Th1 lymphocytes and production of IgG2 antibodies in vivo. Saanen goats co-immunized with recombinant vaccinia viruses expressing caprine IL-12 (rRB-IL12) and the caprine arthritis-encephalitis virus (CAEV) envelope (env) gene (rWR-63) were evaluated for development of immune responses to the CAEV env encoded surface glycoprotein (SU). Immune responses were defined by: (i) SU antibody titers; (ii) the ratio of SU IgG1 and IgG2 antibodies; (iii) interferon gamma (IFNgamma) and IL-4 gene expression and proliferative response of SU stimulated lymph node mononuclear cells (LNMC). Apart from enhancement of IFNgamma and IL-4 gene expression in SU stimulated LNMC, rRB-IL12 did not affect the immune response to rWR-63 encoded SU. Thus, localized production of exogenous species specific IL-12 at the site of immunization did not focus initial priming of antigen reactive Th lymphocytes. These results are in contrast to previous studies using inbred mice and raise questions regarding the use of cytokine adjuvants to focus immune responses in outbred animals.

Animals↗

The role of laboratory investigation in the diagnosis and management of patients with suspected herpes simplex encephalitis: a consensus report. The EU Concerted Action on Virus Meningitis and Encephalitis.

As effective therapies for the treatment of herpes simplex encephalitis (HSE) have become available, the virology laboratory has acquired a role of primary importance in the early diagnosis and clinical management of this condition. Several studies have shown that the polymerase chain reaction (PCR) of CSF for the detection of herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) DNA provides a reliable method for determining an aetiological diagnosis of HSE. The use of PCR in combination with the detection of a specific intrathecal antibody response to HSV currently represents the most reliable strategy for the diagnosis and monitoring of the treatment of adult patients with HSE. The use of these techniques has also led to the identification of atypical presentations of HSV infections of the nervous system and permits the investigation of patients who develop a relapse of encephalitic illness after an initial episode of HSE. A strategy for the optimal use of the investigative laboratory in the diagnosis of HSE and subsequent management decisions is described.

Acyclovir↗

Encephalitis after hepatitis B vaccination: recurrent disseminated encephalitis or MS?

OBJECTIVE: To describe clinical and MRI features of patients with a disease suggestive of CNS inflammation after hepatitis B vaccination. METHODS: Eight patients with confirmed CNS inflammation occurring less than 10 weeks after hepatitis B vaccination are described. They received follow-up clinically and on MRI for a mean period of 18 months. RESULTS: Clinical and MRI findings were compatible with acute disseminated encephalomyelitis. However, clinical follow-up, repeated MRI, or both showed the persistence of inflammatory activity, which makes this encephalitis more suggestive of MS than of acute disseminated encephalomyelitis. CONCLUSION: The persistent inflammatory activity observed clinically and on MRI in these patients is comparable with that usually observed in MS. Epidemiologic studies are currently testing the hypothesis of a triggering role of hepatitis B vaccination in CNS demyelination.

Adult↗

Japanese encephalitis surveillance in China (Province of Taiwan) during 1968-1971. II. Age-secific incidence in connection with Japanese encephalitis vaccination program.

A baseline age/morbidity pattern for Japanese encephalitis (JE) epidemic in China (Province of Taiwan) in the 1960s was sought in JE surveillance. The pattern is characterized by: (1) high incidence in age groups 2-4 years, (2) moderately high incidence in age groups 5-7 years, (3) negligible incidence in children under 1 year of age as well as in adults, and (4) the variability of relative height of peak incidence co-incident with the JE-epidemic size in situ. Concurrently with surveillance, a JE-vaccination program was implemented by the Government. The children of target age groups received two doses of vaccine each during April. Vigilant supervision was given to the campaign to achieve a high coverage rate with two-dose vaccination and meticulous record-keeping. During 1969-1972, 2-year olds were the exclusive target; 52.2% (1969), 71.5% (1970), 74.5% (1971), and 83.0% (1972) of the target age group were covered. A considerable change from the baseline age/morbidity pattern seen in 1968 occurred during the above period. The comparison of epidemicity-adjusted incidence by year indications that incidence reduction in the 2- and 3-year old children in 1971 were substantial and suggests the possible impact of vaccination. The total JE incidence for the period 1968-1971 appears to be much lower in vaccinated population (23 reported and 8 confirmed/0.9 million) than in unvaccinated population (1,330 reported and 679 confirmed/2.2 million).

Age Factors↗

Japanese encephalitis virus infection in fetal mice at different stages of pregnancy. II. Resistance to Japanese encephalitis virus infection.

The relationship between the stage of pregnancy of mice at the time of Japanese encephalitis (JE) virus inoculation and the resistance of JE virus infection of their offsprings was investigated. It was found that there was a stronger resistance to JE virus infection in offsprings born of mothers inoculated with JE virus at nine to sixteen days before parturition than in offsprings of mothers inoculated at one to eight days or at seventeen to twenty days before parturition. Resistance of the offsprings to JE virus infection lasted up to the age of 180 days after birth.

Animals↗

Partial nucleotide sequence of Japanese encephalitis virus ling strain genome and comparison of the encoded structural proteins and nonstructural protein NS1 among Japanese encephalitis virus strains.

Approximately 4000 nucleotides of the 5'-terminal portion of Japanese encephalitis virus (JEV) Ling strain genome were cloned and sequenced. This nucleotide sequence and its encoded C-PrM-E-NS1 polyprotein sequences were also compared with the corresponding sequences of other JE virus strains. Results demonstrated that the nucleotide sequence homology varied from 97.1 to 99.3% and the amino acid homology 98.6 to 98.9%. Based on homology, the Ling strain was closer to the Beijing-1 strain than to the SA14 and JaOArS982 strains. However, only on comparison of the E sequence, which neutralization, hemagglutination-inhibition and complement fixation antigenic determinants are located, between Ling and other JEV strains demonstrated that nucleotide sequence homology varied from 97.1% to 99.3% and amino acid homology from 98.6% to 99.2%. The Ling strain JEV is more closely related to the Beijing-1 strain than to the Nakayama NIH, SA14 and JaOArS982 strains in that order. Based on this analysis, the Taiwanese JEV strain appears to be more closely related to the Chinese strain than to the Japanese strain. Also, JEV strains isolated in humans are more closely related to each other than to JEV strains of mosquito isolates.

Amino Acid Sequence↗