The efficacy of inactivated West Nile vaccine (WN-VAX) in mice and monkeys

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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.

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Most cited references 13

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The outbreak of West Nile virus infection in the New York City area in 1999.

Denis Nash, Farzad Mostashari, Annie Fine … (2001)

In late August 1999, an unusual cluster of cases of meningoencephalitis associated with muscle weakness was reported to the New York City Department of Health. The initial epidemiologic and environmental investigations suggested an arboviral cause. Active surveillance was implemented to identify patients hospitalized with viral encephalitis and meningitis. Cerebrospinal fluid, serum, and tissue specimens from patients with suspected cases underwent serologic and viral testing for evidence of arboviral infection. Outbreak surveillance identified 59 patients who were hospitalized with West Nile virus infection in the New York City area during August and September of 1999. The median age of these patients was 71 years (range, 5 to 95). The overall attack rate of clinical West Nile virus infection was at least 6.5 cases per million population, and it increased sharply with age. Most of the patients (63 percent) had clinical signs of encephalitis; seven patients died (12 percent). Muscle weakness was documented in 27 percent of the patients and flaccid paralysis in 10 percent; in all of the latter, nerve conduction studies indicated an axonal polyneuropathy in 14 percent. An age of 75 years or older was an independent risk factor for death (relative risk adjusted for the presence or absence of diabetes mellitus, 8.5; 95 percent confidence interval, 1.2 to 59.1), as was the presence of diabetes mellitus (age-adjusted relative risk, 5.1; 95 percent confidence interval, 1.5 to 17.3). This outbreak of West Nile meningoencephalitis in the New York City metropolitan area represents the first time this virus has been detected in the Western Hemisphere. Given the subsequent rapid spread of the virus, physicians along the eastern seaboard of the United States should consider West Nile virus infection in the differential diagnosis of encephalitis and viral meningitis during the summer months, especially in older patients and in those with muscle weakness.

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Report on a WHO consultation on immunological endpoints for evaluation of new Japanese encephalitis vaccines, WHO, Geneva, 2-3 September, 2004.

Ichiro Kurane, Tom Solomon, Julie Jacobson … (2005)

The World Health Organization (WHO) is undertaking consultations on immunological responses as parameters for evaluation and licensure of new Japanese encephalitis (JE) vaccines. Immunological markers could be used by vaccine developers and regulatory authorities to assess vaccine efficacy in absence of clinical efficacy data. The consultation which is reported here reviewed current data on mechanisms of protective immunity gathered from animal experimentation, clinical data from licensed vaccines and from vaccine candidates still in clinical development. Immunological assays and readouts for use in evaluation of candidate vaccines were also discussed. The consultation made a series of recommendations for specifications on immunological criteria to assess JE vaccine efficacy. More detailed recommendations will be drafted following further consultations to serve as WHO guidelines for evaluation and licensure for new JE vaccines.

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ChimeriVax-West Nile virus live-attenuated vaccine: preclinical evaluation of safety, immunogenicity, and efficacy.

Marion S. Ratterree, James W Trent, Juan Arroyo … (2004)

The availability of ChimeriVax vaccine technology for delivery of flavivirus protective antigens at the time West Nile (WN) virus was first detected in North America in 1999 contributed to the rapid development of the vaccine candidate against WN virus described here. ChimeriVax-Japanese encephalitis (JE), the first live- attenuated vaccine developed with this technology has successfully undergone phase I and II clinical trials. The ChimeriVax technology utilizes yellow fever virus (YF) 17D vaccine strain capsid and nonstructural genes to deliver the envelope gene of other flaviviruses as live-attenuated chimeric viruses. Amino acid sequence homology between the envelope protein (E) of JE and WN viruses facilitated targeting attenuating mutation sites to develop the WN vaccine. Here we discuss preclinical studies with the ChimeriVax-WN virus in mice and macaques. ChimeriVax-WN virus vaccine is less neurovirulent than the commercial YF 17D vaccine in mice and nonhuman primates. Attenuation of the virus is determined by the chimeric nature of the construct containing attenuating mutations in the YF 17D virus backbone and three point mutations introduced to alter residues 107, 316, and 440 in the WN virus E protein gene. The safety, immunogenicity, and efficacy of the ChimeriVax-WN(02) vaccine in the macaque model indicate the vaccine candidate is expected to be safe and immunogenic for humans.

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Author and article information

Contributors

Yuko Muraki: ymuraki@mail.biken.or.jp

Takeshi Fujita: tfujita@mail.biken.or.jp

Masaaki Matsuura: mmatsuura@mail.biken.or.jp

Isao Fuke: ifuke@mail.biken.or.jp

Sadao Manabe: smanabe@mail.biken.or.jp

Toyokazu Ishikawa: toishika@mail.biken.or.jp

Yoshinobu Okuno: yokuno@mail.biken.or.jp

Kouichi Morita: moritak@nagasaki-u.ac.jp

Journal

Journal ID (nlm-ta): Virol J

Journal ID (iso-abbrev): Virol. J

Title: Virology Journal

Publisher: BioMed Central (London )

ISSN (Electronic): 1743-422X

Publication date (Electronic): 9 April 2015

Publication date PMC-release: 9 April 2015

Publication date Collection: 2015

Volume: 12

Electronic Location Identifier: 54

Affiliations

[ ]Kanonji Institute, The Research Foundation for Microbial diseases of Osaka University, Yahata-cho 2-9-41, Kannonnji City, Kagawa 768-0061 Japan

[ ]Department of Virology, Institute of Tropical Medicine, Nagasaki University, Sakamoto-machi 1-12-4, Nagasaki City, Nagasaki 852-8523 Japan

Article

Publisher ID: 282

DOI: 10.1186/s12985-015-0282-8

PMC ID: 4403780

PubMed ID: 25889682

SO-VID: 79e4189b-7813-4ef9-8de3-04d53981b327

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 2 October 2014

Date accepted : 18 March 2015

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ScienceOpen disciplines: Microbiology & Virology

Keywords: west nile virus,formalin-inactivated vaccine,challenge test in mouse,efficacy in monkey

Data availability:

ScienceOpen disciplines: Microbiology & Virology

Keywords: west nile virus, formalin-inactivated vaccine, challenge test in mouse, efficacy in monkey

The efficacy of inactivated West Nile vaccine (WN-VAX) in mice and monkeys

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Abstract

Background

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Role of Microbes in Soil Fertility and Human Health

Most cited references 13

The outbreak of West Nile virus infection in the New York City area in 1999.

Report on a WHO consultation on immunological endpoints for evaluation of new Japanese encephalitis vaccines, WHO, Geneva, 2-3 September, 2004.

ChimeriVax-West Nile virus live-attenuated vaccine: preclinical evaluation of safety, immunogenicity, and efficacy.

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