The Virulence of West Nile Virus and TP 21 Virus and Their Application to a Group B Arbor Virus Vaccine

Abstract

Summary Spider monkeys and chimpanzees were given a series of three injections consisting of 17D yellow fever virus, followed by living West Nile virus, followed by a third injection which consisted of formalin-inactivated Russian spring-summer virus vaccine. On the basis of neutralizing antibody responses, the limitation of viremia, or both, developing when the animals were challenged with virulent viruses, these primates were judged to be protected to a considerable extent against Japanese B encephalitis, West Nile virus, St. Louis encephalitis, Murray Valley encephalitis virus, dengue types 1, 2, 3, and 4, two antigenic types of the Russian spring-summer virus complex, and Wesselsbron virus. An isolate of West Nile virus was passed a number of times in chick embryo tissue cultures and purified by the plaque technique. The progeny of two virus plaques, in a concentration of 106 mouse intracerebral lethal doses, did not produce encephalitis in intracerebrally inoculated rhesus monkeys. These attenuated viral preparations, on the basis of intracerebral titrations in mice, had at least 1,000 times the virus concentration that was necessary to produce encephalitis with the parent type. One of these attenuated isolates still produced homologous and heterologous neutralizing antibodies comparable to those of the parent strain. The data indicate that this attenuated West Nile virus did not revert to a more virulent form after alternate intracerebral passages in rhesus monkeys and suckling mice. The TP-21 strain of the Russian spring-summer virus complex was passed a number of times in chick embryo tissue cultures and purified by the plaque technique. The progeny from one of the virus plaques, in a concentration of approximately 300,000 mouse i.c. LD50, did not produce encephalitis when inoculated intracerebrally into rhesus monkeys. When this purified virus isolate of TP-21 was substituted for the formalin-inactivated Russian spring-summer vaccine in the triple vaccination procedure, considerable protection was noted in spider monkeys challenged with four members of the Russian spring-summer group of viruses.