Page 111 - VHSA - Onderstepoort 100 Years - Part 3

of the epidemiological features of both diseases such as their seasonal nature and geographical distribution (see also Part 3: Parasitology).
Initially the vaccine contained four virus strains and with time more strains were added. Fear was expressed that neurotropic adaptation of this virus to the mouse may also lead to potential neurotropism in the horse. To counter these fears Alexander selected one of the four vaccine strains and inoculated several horses intracerebrally. Although the horses developed definite neurological signs, none died and Alexander concluded that if direct inoculation into the brain did not kill horses, subcutaneous inoculation should be perfectly safe. However, work done 30 years later proved that, had any of the other three
vaccine strains been chosen, the outcome
of the experiment might have been entirely
different.
ONDERSTEPOORT 100
6 vaccine strain which explained the success achieved with the use of the polyvalent vaccine. A monovalent serotype 6 AHS vaccine (using the Onderstepoort vaccine strain) was subsequently produced in Teheran until a vaccine against serotype 9 was developed.
Despite the vaccine’s efficacy in combating the outbreak, alarming reports of neurological signs, including blindness, were received from various countries. These complications were most prevalent in donkeys and occurred on average between 4 and 6 weeks post-vaccination. Despite strong circumstantial evidence incriminating the AHS vaccine, Alexander found it very difficult to reconcile these alarming findings with his experience with the AHS vaccine and blamed
In general the immunization of horses
and mules with neurotropic AHS vaccine
has been satisfactory and the use of this
vaccine on a large scale revolutionized
the control of horsesickness. Failures were
usually due to virus strains not represented
in the vaccine. Such new strains were duly
attenuated and also incorporated in the
vaccine. By 1949 the vaccine contained
eight strains (not necessarily serotypes).
The neurotropic vaccine was used to great
effect, not only in South Africa but also
elsewhere in Africa. During the 1944
epizootic of AHS in North Africa and the
Near East it was used to immunize horses, mules and donkeys and resulted in complete control of the epizootic.
In 1951 McIntosh took over the AHS research from Alexander. He improved the neutralization test considerably by using hyperimmune rabbit serum instead of horse serum. He conducted extensive immunological studies on 42 virus isolates, including the eight vaccine strains, and various other isolates from cases of AHS in immunized horses. The results indicated that the eight vaccine strains belonged to six serotypes and several of the isolates from immunized horses belonged to a seventh serotype. The Karen isolate, which originated from Kenya in 1952, was selected as prototype for serotype 7.
Howell succeeded McIntosh in 1957 and continued the AHS work. In 1958 he isolated an additional serotype (Type 8). Following the serious outbreak of AHS in 1960 in the Near and Middle East, he was deputized to assist with the diagnosis and control of the disease. A new serotype (serotype 9) was identified by Howell. The polyvalent AHS vaccine from Onderstepoort (containing serotypes 1 to 7) was used extensively in the Near and Middle East countries and assisted greatly in reducing losses which led to the eventual eradication of the disease. It was established that the causative virus (serotype 9) was serologically closely related to the serotype
“The polyvalent AHS vaccine from Onderstepoort (containing serotypes 1 to 7) was used extensively in the Near and Middle East countries and assisted greatly in reducing losses which led to the eventual eradication of African horsesickness.”
it on unknown local infections such as the recently described “Near East Equine Encephalitis” (which eventually proved to be rabies). However, despite several requests to the relevant authorities, no brain samples from affected animals were received and consequently the role of AHS vaccination in the aetiology of the neural syndrome could not be established.
In January 1961 Erasmus was given the responsibility for AHS diagnosis, research and vaccine production. The neurotropic vaccine was produced in adult mice which meant the weekly intracerebral inoculation of thousands of mice with each serotype and 2-3 days later the harvesting of their brains. For the first 2 years this laborious activity consumed all his time but fortunately relief
came at the end of 1962 when the production of this vaccine
was taken over by van Rooyen and his technical team. 201
During 1962 Erasmus discovered that following intra- peritoneal inoculation of guinea pigs, the Karen vaccine virus caused fatal encephalitis. In comparing all the vaccine strains, it emerged that the serotype 7 (Karen) strain was markedly more neurotropic than the other vaccine strains and was capable of traversing the blood-brain barrier. It is, therefore, highly likely that the Karen strain was responsible for the post-vaccinal neurological reactions observed in the Middle East. Further work in guinea pigs indicated that all seven vaccine strains possessed neurotropic potential for the guinea pig brain depending upon the route of virus administration. The intranasal route proved to be the most sensitive and using this route the Karen strain produced fatal encephalitis in horses and dogs. In the light of this information the Karen strain was omitted from the vaccine and the need for a safe and efficacious alternative to the neurotropic vaccine was emphasized.
Studies by Erasmus on the pathogenesis of AHS in horses revealed virus replication in various lymphoid and other tissues prior to the appearance of virus in the blood stream. It further strengthened the concept of the existence of a mixed virus population as far as cell or tissue tropism was concerned. Serial
Virology
1908-2008
Years