The Virulence of West Nile Virus and TP 21 Virus and Their Application to a Group B Arbor Virus Vaccine *
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SummarySpider 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.Keywords:
Viremia
Flavivirus
Attenuated vaccine
West Nile virus disease (WND) is an arthropod-borne zoonosis responsible for nonspecific fever or severe encephalitis. The pathogen is West Nile virus belonging to the genus Flavivirus, family Flaviviridae. Every year, thousands of cases were reported, which poses significant public health risk. Here, we constructed a West Nile virus chimera, ChiVax-WN01, by replacing the prMΔE gene of JEV SA14-14-2 with that of the West Nile virus NY99. The ChiVax-WN01 chimera showed clear, different characters compared with that of JEV SA14-14-2 and WNV NY99 strain. An animal study indicated that the ChiVax-WN01 chimera presented moderate safety and immunogenicity for 4-week female BALB/c mice.
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A bstract : Although there are approximately 68 flaviviruses recognized, vaccines have been developed to control very few human flavivirus diseases. Licensed live attenuated vaccines have been developed for yellow fever (strain 17D) and Japanese encephalitis (strain SA14‐14‐2) viruses, and inactivated vaccines have been developed for Japanese encephalitis and tick‐borne encephalitis viruses. The yellow fever live attenuated 17D vaccine is one of the most efficacious and safe vaccines developed to date and has been used to immunize more than 300 million people. A number of experimental vaccines are being developed, most notably for dengue. Candidate tetravalent live attenuated dengue vaccines are undergoing clinical trials. Other vaccines are being developed using reverse genetics, DNA vaccines, and recombinant immunogens. In addition, the yellow fever 17D vaccine has been used as a backbone to generate chimeric viruses containing the premembrane and envelope protein genes from other flaviviruses. The “Chimerivax” platform has been used to construct chimeric Japanese encephalitis and dengue viruses that are in different phases of development. Similar strategies are being used by other laboratories.
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Many viruses belonging to the Flaviviridae family are transmitted by invertebrate vectors. Among those transmitted by mosquitos, there are many human pathogens of great medical importance, such as Japanese encephalitis virus, West Nile virus, dengue virus, Zika virus, or yellow fever virus. Millions of people contract mosquito-borne diseases each year, leading to thousands of deaths. Co-circulation of genetically similar flaviviruses in the same areas result in the generation of crossreactive antibodies, which is of serious concern for the development of effective vaccines and diagnostic tests. This review provides comprehensive insight into the potential use of virus-like particles as safe and effective antigens in both diagnostics tests, as well as in the development of vaccines against several mosquito-borne flaviviruses.
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日本脑炎病毒(JEV ) 与包括黄发烧病毒，登革热病毒和韦斯特尼罗河病毒的人的病原体有关仔细是忍受蚊子的 flavivirus。当前为所有 flavivirus 没有有效抗病毒的治疗，仅仅一些高度有效的疫苗为人的使用被准许。在这份报纸，六 heterologous flaviviruses (DENV1-4， WNV 和 JEV ) 的 E 蛋白质领域 III (DIII ) 成功地在 Escherichia coli 被表示。蛋白质在增溶和 refolding 过程以后被净化，由 SDS 页并且西方的弄污描绘了。竞争抑制证明所有 recombinant flavivirus DIII 蛋白质堵住了 JEV 的入口进 BHK-21 房间。进一步的研究显示可溶的 recombinant flavivirus DIII 导致的抗体部分保护了老鼠免于致命的 JEV 挑战。这些结果证明 recombinant flavivirus DIII 蛋白质能竞争地禁止 JEV 感染，并且有合适的合拢的 flavivirus DIII 的免疫导致了对在老鼠的 JEV 感染跨保护，暗示 DIII 的一个可能的角色为在象它在为在动物模型的免疫的抗原的使用一样的 flavivirus 之中跨保护。
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Journal Article Vector Competence of Argentine Mosquitoes (Diptera: Culicidae) for West Nile virus (Flaviviridae: Flavivirus) Get access María V. Micieli, María V. Micieli 1Centro de Estudios Parasitológicos y de Vectores (CONICET-CCT-La Plata, Universidad Nacional de La Plata). Calle 2 N° 584, 1900, La Plata, Argentina. Search for other works by this author on: Oxford Academic PubMed Google Scholar Amy C. Matacchiero, Amy C. Matacchiero 2New York State Department of Health, Wadsworth Center, 5668 State Farm Rd., Slingerlands, NY 12159. Search for other works by this author on: Oxford Academic PubMed Google Scholar Evangelina Muttis, Evangelina Muttis 1Centro de Estudios Parasitológicos y de Vectores (CONICET-CCT-La Plata, Universidad Nacional de La Plata). Calle 2 N° 584, 1900, La Plata, Argentina. Search for other works by this author on: Oxford Academic PubMed Google Scholar Dina M. Fonseca, Dina M. Fonseca 3Center for Vector Biology, Rutgers University, 180 Jones Ave., New Brunswick, NJ 08901. Search for other works by this author on: Oxford Academic PubMed Google Scholar Matthew T. Aliota, Matthew T. Aliota 2New York State Department of Health, Wadsworth Center, 5668 State Farm Rd., Slingerlands, NY 12159. Search for other works by this author on: Oxford Academic PubMed Google Scholar Laura D. Kramer Laura D. Kramer 5 2New York State Department of Health, Wadsworth Center, 5668 State Farm Rd., Slingerlands, NY 12159.4School of Public Health, State University of New York at Albany, Department of Biomedical Sciences, Center for Medical Sciences, P.O. Box 22002, Albany, NY 12201-02002. 5Corresponding author, e-mail: kramer@wadsworth.org. Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Medical Entomology, Volume 50, Issue 4, 1 July 2013, Pages 853–862, https://doi.org/10.1603/ME12226 Published: 01 July 2013 Article history Received: 10 October 2012 Accepted: 17 April 2013 Published: 01 July 2013
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The sudden dramatic emergence of the mosquito transmitted flavivirus Zika virus has bought to the world's attention a relatively obscure virus that was previously only known to specialist researchers. The genus Flavivirus of the family Flaviviridae contains a number of well-known mosquito transmitted human pathogenic viruses including the dengue, yellow fever, Japanese encephalitis and West Nile viruses. However, the genus also contains a number of lesser known human pathogenic viruses transmitted by mosquitoes including Wesselsbron virus, Ilheus virus, St. Louis encephalitis virus and Usutu virus. This review summarizes our knowledge of these lesser known mosquito transmitted flaviviruses and highlights their potential to emerge.
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The genus Flavivirus of the family Flaviviridae comprises over 70 viruses,
many of which, such as the Dengue (DEN) virus, Japanese Encephalitis (JE) virus,
West Nile virus (WNV), St. Louis Encephalitis (SLE) virus, and Yellow fever (YF)
virus are important human pathogens. Flavivirus can be transmitted to humans via
either a mosquito or tick vector. The flavivirus genera are of importance to the
medical community because they have been found to be the causative agent of many
endemic and epidemic illnesses across the world. Japanese Encephalitis virus (JEV)
is the most important cause of viral encephalitis in Asia based on its frequency and
severity. With the near eradication of poliomyelitis, JEV is now the leading cause of
childhood viral neurological infection and disability in Asia.
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