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      Immunization with West Nile virus envelope domain III protects mice against lethal infection with homologous and heterologous virus

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          Summary

          The Japanese encephalitis virus (JEV) serocomplex-group consists of mosquito-borne flaviviruses, which include West Nile virus (WNV) and JEV, and both may cause severe encephalitis in humans. WNV has spread rapidly across the United States since its introduction in 1999 and its geographical distribution within the western hemisphere is expected to further expand, whereas, JEV is the most common cause of viral encephalitis in Southeast Asia, China and India. Currently, there is no registered human vaccine or specific therapy to prevent or treat WNV infection. Here we describe the efficacy of recombinant domain III (DIII) of WNV glycoprotein E in a mouse model. It induces high neutralizing antibody titers, as well as, protection against lethal WNV infection in C57BL/6 mice. This vaccine preparation also afforded partial protection against lethal JEV infection.

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          Transmission of West Nile virus through blood transfusion in the United States in 2002.

          Lisa N Pealer, Anthony Marfin, Lyle Petersen … (2003)
          During the 2002 West Nile virus epidemic in the United States, patients were identified whose West Nile virus illness was temporally associated with the receipt of transfused blood and blood components. Patients with laboratory evidence of recent West Nile virus infection within four weeks after receipt of a blood component from a donor with viremia were considered to have a confirmed transfusion-related infection. We interviewed the donors of these components, asking them whether they had had symptoms compatible with the presence of a viral illness before or after their donation; blood specimens retained from the time of donation and collected at follow-up were tested for West Nile virus. Twenty-three patients were confirmed to have acquired West Nile virus through transfused leukoreduced and nonleukoreduced red cells, platelets, or fresh-frozen plasma. Of the 23 recipients, 10 (43 percent) were immunocompromised owing to transplantation or cancer and 8 (35 percent) were at least 70 years of age. Immunocompromised recipients tended to have longer incubation periods than nonimmunocompromised recipients and infected persons in mosquito-borne community outbreaks. Sixteen donors with evidence of viremia at donation were linked to the 23 infected recipients; of these donors, 9 reported viral symptoms before or after donation, 5 were asymptomatic, and 2 were lost to follow-up. Fever, new rash, and painful eyes were independently associated with being an implicated donor with viremia rather than a donor without viremia. All 16 donors were negative for West Nile virus-specific IgM antibody at donation. Transfused red cells, platelets, and fresh-frozen plasma can transmit West Nile virus. Screening of potential donors with the use of nucleic acid-based assays for West Nile virus may reduce this risk. Copyright 2003 Massachusetts Medical Society
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            CpG Oligodeoxynucleotides Act as Adjuvants that Switch on T Helper 1 (Th1) Immunity

            Rose Chu, Oleg S. Targoni, Arthur Krieg … (1997)
            Synthetic oligodeoxynucleotides (ODN) that contain unmethylated CpG motifs (CpG ODN) induce macrophages to secrete IL-12, which induces interferon (IFN)-γ secretion by natural killer (NK) cells. Since these cytokines can induce T helper 1 (Th1) differentiation, we examined the effects of coadministered CpG ODN on the differentiation of Th responses to hen egg lysozyme (HEL). In both BALB/c (Th2-biased) and B10.D2 (Th1-biased) mice, immunization with HEL in incomplete Freund's adjuvant (IFA) resulted in Th2-dominated immune responses characterized by HEL-specific secretion of IL-5 but not IFN-γ. In contrast, immunization with IFA-HEL plus CpG ODN switched the immune response to a Th1-dominated cytokine pattern, with high levels of HEL-specific IFN-γ secretion and decreased HEL-specific IL-5 production. IFA-HEL plus CpG ODN also induced anti-HEL IgG2a (a Th1-associated isotype), which was not induced by IFA-HEL alone. Control non–CpG ODN did not induce IFN-γ or IgG2a, excepting lesser increases in B10.D2 (Th1-biased) mice. Thus, CpG ODN provide a signal to switch on Th1-dominated responses to coadministered antigen and are potential adjuvants for human vaccines to elicit protective Th1 immunity.
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              Structural basis of West Nile virus neutralization by a therapeutic antibody

              Grant Nybakken, Theodore Oliphant, Syd Johnson … (2005)
              Pushing the envelope West Nile virus is closely related to the human epidemic-causing dengue, yellow fever and Japanese encephalitis viruses. The study of a particularly effective monoclonal antibody, capable of protecting mice from lethal West Nile virus challenge even if administered 5 days after infection, has provided important information on the structural basis of viral neutralization. The work highlights the domain III region of the viral envelope protein as a potential target for both therapeutic antibodies and vaccines. Supplementary information The online version of this article (doi:10.1038/nature03956) contains supplementary material, which is available to authorized users.
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                Author and article information

                Contributors
                Albert D.M.E. Osterhaus
                Journal
                Journal ID (nlm-ta): Vaccine
                Journal ID (iso-abbrev): Vaccine
                Title: Vaccine
                Publisher: Elsevier Ltd.
                ISSN (Print): 0264-410X
                ISSN (Electronic): 1873-2518
                Publication date PMC-release: 20 November 2007
                Publication date (Print): 10 January 2008
                Publication date (Electronic): 20 November 2007
                Volume: 26
                Issue: 2
                Pages: 153-157
                Affiliations
                [a ]Erasmus Medical Center, Institute of Virology, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands
                [b ]The National Institute of Public Health and the Environment, 3720 BA Bilthoven, The Netherlands
                Author notes
                [* ]Corresponding author. Tel.: +31 10 408 8066; fax: +31 10 408 9485. a.osterhaus@ 123456erasmusmc.nl
                Article
                Publisher ID: S0264-410X(07)01247-9
                DOI: 10.1016/j.vaccine.2007.10.055
                PMC ID: 7127062
                PubMed ID: 18069096
                SO-VID: 02c5532d-a1fe-4774-82b9-a1ca91ddd417
                Copyright © Copyright © 2007 Elsevier Ltd. All rights reserved.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 14 August 2007
                Date revision received : 19 October 2007
                Date accepted : 25 October 2007
                Categories
                Subject: Article

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: west nile virus,domain iii,vaccine,c57bl/6 mice,cross-protection,japanese encephalitis virus
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: west nile virus, domain iii, vaccine, c57bl/6 mice, cross-protection, japanese encephalitis virus

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