West Nile Infection Research Articles

Challenge of Monkeys with Japanese B Virus after Immunization by West Nile Infection Plus Japanese B Vaccine

Summary Treatment of monkeys with various doses of cortisone followed by subcutaneous inoculation of JBE virus led to viremia in each instance but not to clinical disease. Monkeys inoculated with a dose of 0.1 ml of a 10-1 dilution of WN virus for immunization showed viremia within the first 3 days. Neutralizing antibodies to WN virus frequently developed by the 7th day after inoculation and reached their maximum titer in the 2nd and 3rd week. The injection of potent JBE vaccine in WN immune animals had a booster effect on WN neutralizing antibodies. There was a significant rise in JBE neutralizing antibodies in these stone animals after the JBE vaccine inoculation, and 2 out of 3 also developed CF antibodies. Monkeys thus immunized basically with WN virus infection and supplemented with one injection of potent JBE vaccine developed either a questionable degree of viremia or none when inoculated with JBE virus after cortisone treatment. On the other hand, monkeys immunized with one injection of potent JBE vaccine only, or with WN virus only, had a consistent and prolonged viremia. The combined WN and JBE vaccine immunization appeared to prevent infection entirely, since this group of animals showed no serological rises following virus challenge. It is concluded that this evidence, supplementing that obtained with hamsters, recommends this method of immunization for human trial, providing that a safe strain of WN virus for human use is found.

Challenge of Hamsters with Japanese B, St. Louis and Murray Valley Encephalitis Viruses after Immunization by West Nile Infection Plus Specific Vaccine

Summary and Conclusions Groups of hamsters were basically immunized with active WN virus following administration of WN inactivated vaccine. Most of these animals were given 1 or 2 supplementary injections of formalin inactivated vaccines of JBE, SLE or MVE viruses. Others were given 1 to 3 injections of vaccine without the preceding WN immunization. Groups of animals with these various immunization schedules were then challenged subcutaneously in a quantitative manner with JBE, SLE or MVE virus, depending on the virus vaccine used. For JBE and SLE virus challenge the animals were treated with cortisone to render them susceptible to peripheral inoculation. Quantitative neutrahzation and complement fixation tests against WN and one or more other viruses were made on sera drawn from animals of the various groups just prior to virus challenge. In general, the character of challenge and serological responses was similar with all viruses. WN infection plus 1 injection of vaccine always afforded better protection than 1 injection of vaccine alone and usually gave protection equal to or better than that obtained after 3 injections of vaccine. Neutralizing antibody titers showed an association with protection as afforded by inactivated virus vaccine of homologous type when used alone. Occasionally, however, those animals with WN virus plus vaccine, the group which was most resistant, did not have the highest neutralization index. Complement-fixing antibodies were never detected after vaccine alone, but appeared only in animals which had had a preceding infection with active WN virus. Detectable complement-fixing antibody response to the virus of the type represented by the vaccine appeared to correlate best with maximum protection. Among the 3 viruses used, the most striking difference observed in protection against challenge occurred between the groups tested with JBE or SLE viruses and those with MVE. The latter resisted challenge to a much greater extent after all types of immunizing procedures. This was attributed in large part to the fact that cortisone was not used during challenge with MVE virus. It was suggested that cortisone interfered with the booster response ordinarily associated with infection in a partially immunized animal. Immunity in a naturally susceptible host, such as man, it was predicted, would probably be of a higher order for JBE and SLE than that observed in cortisone treated hamsters. Results should parallel those of hamsters challenged with MVE—a situation in which cortisone was not needed. Parallels have been pointed out between the serological responses occurring in hamsters and man after a variety of immunological experiences with hve and inactivated agents of Group B, singly and in combination. It is concluded that when and if a suitably benign or attenuated strain of WN virus becomes available for safe administration to man as a basic immunizing procedure to these Group B viruses, one or more subsequent injections of inactivated vaccine of the virus type against which protection is desired should provide better immunity than vaccine alone.

A study of the ecology of West Nile virus in Egypt.

Summary and Conclusions The results are recorded of an investigation of the geographical distribution of West Nile virus in Egypt and the southern Sudan, the epidemiology of human infection, and the general ecology of the virus in the Nile Delta, as revealed by virus isolations, surveys for specific antibodies and study of the biological environment. According to serological surveys the virus is widely disseminated along the Egyptian Nile and in the southern Sudan; 61 per cent of 1168 human bloods collected in Egypt and 40 per cent of 350 collected in the Sudan neutralized WN virus. In an endemic area in the Nile Delta where the intensive studies were conducted, West Nile infection is essentially a childhood disease with yearly peaks of transmission during mid-summer. No reliable information on the symptomatology of the infection in children was obtained, but the impression was gained that it is a self-limited, non-fatal febrile disease rarely associated with definite manifestations of encephalitis. The virus was repeatedly isolated from the blood of febrile children (23) and from mosquitoes, Culex univittatus (12) and Culex antennatus (5), twice from pigeons (Columba livia) and once from the hooded crow (Corvus corone sardonius). The fact that C. univittatus was more frequently found to be infected than any other species of mosquito may be due to its relative predilection for avian blood. None of 530 pools of other arthropods, including ticks, lice, fleas, mites and flies, yielded virus. On both experimental and ecological grounds it is concluded that the main cycle of the virus is probably through mosquitoes and birds in which man may become involved. Serological evidence points to infections of domestic quadrupeds, but these are probably only tangential or dead-end infections. It is likely that non-migratory birds are responsible for the local dissemination of the virus but, as it appears to be endemic in parts of the Nile Delta, its transport over long distances by migratory birds was not investigated. There is evidence for believing that the virus over-winters through a process of retarded transmission by the mosquitoes that remain active throughout the colder months, although the possible role of ticks as a reservoir of the virus should be further investigated. Non-endemicity in the northern rim of the Delta may be accounted for by the less dense human and bird population there and the scarcity of what appears to be the most important vector, C. univittatus.