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      Serological responses in humans to the smallpox vaccine LC16m8

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          Abstract

          In response to potential bioterrorism with smallpox, members of the Japanese Self-Defense Forces were vaccinated with vaccinia virus (VACV) strain LC16m8, an attenuated smallpox vaccine derived from VACV strain Lister. The serological response induced by LC16m8 to four virion-surface proteins and the intracellular mature virus (IMV) and extracellular enveloped virus (EEV) was investigated. LC16m8 induced antibody response against the IMV protein A27 and the EEV protein A56. LC16m8 also induced IMV-neutralizing antibodies, but unlike the VACV strain Lister, did not induce either EEV-neutralizing antibody or antibody to EEV protein B5, except after revaccination. Given that B5 is the only target for EEV-neutralizing antibody and that neutralization of both IMV and EEV give optimal protection against orthopoxvirus challenge, these data suggest that immunity induced by LC16m8 might be less potent than that deriving from strain Lister. This potential disadvantage should be balanced against the advantage of the greater safety of LC16m8.

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          Immunogenicity of a highly attenuated MVA smallpox vaccine and protection against monkeypox.

          Patricia Earl, Jeffrey Americo, Linda Wyatt … (2004)
          The potential use of smallpox as a biological weapon has led to the production and stockpiling of smallpox vaccine and the immunization of some healthcare workers. Another public health goal is the licensing of a safer vaccine that could benefit the millions of people advised not to take the current one because they or their contacts have increased susceptibility to severe vaccine side effects. As vaccines can no longer be tested for their ability to prevent smallpox, licensing will necessarily include comparative immunogenicity and protection studies in non-human primates. Here we compare the highly attenuated modified vaccinia virus Ankara (MVA) with the licensed Dryvax vaccine in a monkey model. After two doses of MVA or one dose of MVA followed by Dryvax, antibody binding and neutralizing titres and T-cell responses were equivalent or higher than those induced by Dryvax alone. After challenge with monkeypox virus, unimmunized animals developed more than 500 pustular skin lesions and became gravely ill or died, whereas vaccinated animals were healthy and asymptomatic, except for a small number of transient skin lesions in animals immunized only with MVA.
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            Vaccinia virus morphogenesis and dissemination.

            Jeffrey Smith, April K. Roberts (2008)
            Vaccinia virus is the smallpox vaccine. It is the most intensively studied poxvirus, and its study has provided important insights about virus replication in general and the interactions of viruses with the host cell and immune system. Here, the entry, morphogenesis and dissemination of vaccinia virus are considered. These processes are complicated by the existence of two infectious vaccinia virus particles, called intracellular mature virus (IMV) and extracellular enveloped virus (EEV). The IMV particle is surrounded by one membrane, and the EEV particle comprises an IMV particle enclosed within a second lipid membrane containing several viral antigens. Consequently, these virions have different biological properties and play different roles in the virus life cycle.
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              Smallpox vaccines: targets of protective immunity.

              Bernard Moss (2010)
              The eradication of smallpox, one of the great triumphs of medicine, was accomplished through the prophylactic administration of live vaccinia virus, a comparatively benign relative of variola virus, the causative agent of smallpox. Nevertheless, recent fears that variola virus may be used as a biological weapon together with the present susceptibility of unimmunized populations have spurred the development of new-generation vaccines that are safer than the original and can be produced by modern methods. Predicting the efficacy of such vaccines in the absence of human smallpox, however, depends on understanding the correlates of protection. This review outlines the biology of poxviruses with particular relevance to vaccine development, describes protein targets of humoral and cellular immunity, compares animal models of orthopoxvirus disease with human smallpox, and considers the status of second- and third-generation smallpox vaccines. Published 2010. This article is a US Government work and is in the public domain in the USA.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Gen Virol
                Journal ID (iso-abbrev): J. Gen. Virol
                Journal ID (publisher-id): JGV
                Journal ID (hwp): vir
                Title: The Journal of General Virology
                Publisher: Society for General Microbiology
                ISSN (Print): 0022-1317
                ISSN (Electronic): 1465-2099
                Publication date (Print): October 2011
                Publication date PMC-release: October 2011
                Volume: 92
                Issue: Pt 10
                Pages: 2405-2410
                Affiliations
                [1 ]Section of Virology, Faculty of Medicine, Imperial College London, St Mary’s Campus, Norfolk Place, London W2 1PG, UK
                [2 ]National Institute of Public Health, Department of Policy Sciences, 2-3-6 Minami, Wako-shi, Saitama 351-0197, Japan
                [3 ]Self-Defense Force, Central Hospital, Health Department, Management Division, 1-2-24 Ikejiri, Setagaya, Tokyo 154-8532, Japan
                [4 ]Bio-preparedness Research Laboratory, Department of Tropical Medicine and Parasitology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan
                [5 ]The Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN), 1-6-1 Okubo, Kumamoto 860-8568, Japan
                Author notes
                Correspondence Geoffrey L. Smith geoffrey.l.smith@ 123456imperial.ac.uk
                Article
                Publisher ID: 034207
                DOI: 10.1099/vir.0.034207-0
                PMC ID: 3347799
                PubMed ID: 21715598
                SO-VID: 65682cd4-1370-4b98-8adc-ca1a0c701b92
                Copyright © © 2011 SGM
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 12 May 2011
                Date accepted : 28 June 2011
                Funding
                Funded by: UK Department of Health
                Funded by: Medical Research Council
                Categories
                Subject: Short Communication
                Subject: Animal
                Subject: DNA viruses
                Custom metadata
                CopyEditor Ashreena Osman
                Disc-work Marianne Asbury
                openaccess free
                OpenAccessEmbargo 0

                ScienceOpen disciplines: Microbiology & Virology
                Data availability:
                ScienceOpen disciplines: Microbiology & Virology

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