The efficacy of inactivated West Nile vaccine (WN-VAX) in mice and monkeys
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SHORT REPORT
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The efficacy of inactivated West Nile vaccine (WN-VAX) in mice and monkeys Yuko Muraki1, Takeshi Fujita1, Masaaki Matsuura1, Isao Fuke1, Sadao Manabe1, Toyokazu Ishikawa1, Yoshinobu Okuno1* and Kouichi Morita2
Abstract Background: West Nile virus (WNV) belonging to the genus Flavivirus of the family Flaviviridae causes nervous system disorder in humans, horses and birds. Licensed WNV vaccines are available for use in horses but not for humans. We previously developed an inactivated West Nile virus vaccine (WN-VAX) using a seed virus from West Nile virus (WNV NY99) that was originally isolated in New York City in 1999. In this study, we report the immunogenicity of WN-VAX in both mice and non-human primates. Findings: The WN-VAX immunized mice showed protection against lethal infection with WNV NY99. The challenge test performed on mice passively immunized with serum from other mice that were previously immunized with WN-VAX confirmed that the neutralizing antibody titers of more than 1log10 protected the passively immunized mice from WNV lethal infection. Furthermore, monkeys (Macaca fascicularis) immunized three times with 2.5 μg, 5 μg or 10 μg/dose of WN-VAX exhibited neutralizing antibodies in their sera with titers of more than 2log10 after the second immunization. Conclusions: The WN-VAX was protective in mice both by active and passive immunizations and was immunogenic in monkeys. These results suggest that the vaccine developed in this study may be a potential WNV vaccine candidate for human use. Keywords: West Nile Virus, Formalin-inactivated vaccine, Challenge test in mouse, Efficacy in monkey
Findings Background
West Nile virus (WNV) belonging to the genus Flavivirus of the family Flaviviridae has caused sporadic disease epidemics in Africa, Europe, Middle East and West Asia. Until the end of the 1990s, WNV disease was not taken seriously because it was believed to be a mild febrile infection. Later, this virus was found to be highly pathogenic to humans, horses and birds. A strain of this virus that spread in New York over a short period of time was isolated [1]. This strain has caused high rates of nervous system disorder and mortality, particularly in the elderly population [2]. There are commercially available licensed WNV vaccines for horses, but there are currently none available for humans. Candidate vaccines, such as the chimera vaccine * Correspondence: [email protected] 1 Kanonji Institute, The Research Foundation for Microbial diseases of Osaka University, Yahata-cho 2-9-41, Kannonnji City, Kagawa 768-0061, Japan Full list of author information is available at the end of the article
with YFV, inactivated vaccine and DNA vaccine, for human use are still under development (Table 1) [3-6]. We previously reported the development of an inactivated and preservative-free WNV vaccine (WN-VAX) for human use. The method used for the production of this vaccine candidate was similar to that used to produce the cell-culture-derived inactivated Japanese encephalitis (JE)
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