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      Modulating Vaccinia Virus Immunomodulators to Improve Immunological Memory

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The increasing frequency of monkeypox virus infections, new outbreaks of other zoonotic orthopoxviruses and concern about the re-emergence of smallpox have prompted research into developing antiviral drugs and better vaccines against these viruses. This article considers the genetic engineering of vaccinia virus (VACV) to enhance vaccine immunogenicity and safety. The virulence, immunogenicity and protective efficacy of VACV strains engineered to lack specific immunomodulatory or host range proteins are described. The ultimate goal is to develop safer and more immunogenic VACV vaccines that induce long-lasting immunological memory.

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          Most cited references273

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          Recognition of microorganisms and activation of the immune response.

          Ruslan Medzhitov (2007)
          The mammalian immune system has innate and adaptive components, which cooperate to protect the host against microbial infections. The innate immune system consists of functionally distinct 'modules' that evolved to provide different forms of protection against pathogens. It senses pathogens through pattern-recognition receptors, which trigger the activation of antimicrobial defences and stimulate the adaptive immune response. The adaptive immune system, in turn, activates innate effector mechanisms in an antigen-specific manner. The connections between the various immune components are not fully understood, but recent progress brings us closer to an integrated view of the immune system and its function in host defence.
          Article 0 comments Cited 735 times – based on 0 reviews     Review now
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            NK cell recognition.

            Lewis L Lanier (2005)
            The integrated processing of signals transduced by activating and inhibitory cell surface receptors regulates NK cell effector functions. Here, I review the structure, function, and ligand specificity of the receptors responsible for NK cell recognition.
            Article 0 comments Cited 669 times – based on 0 reviews     Review now
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              Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures.

              Richard E. Randall, Stephen Goodbourn (2008)
              The interferon (IFN) system is an extremely powerful antiviral response that is capable of controlling most, if not all, virus infections in the absence of adaptive immunity. However, viruses can still replicate and cause disease in vivo, because they have some strategy for at least partially circumventing the IFN response. We reviewed this topic in 2000 [Goodbourn, S., Didcock, L. & Randall, R. E. (2000). J Gen Virol 81, 2341-2364] but, since then, a great deal has been discovered about the molecular mechanisms of the IFN response and how different viruses circumvent it. This information is of fundamental interest, but may also have practical application in the design and manufacture of attenuated virus vaccines and the development of novel antiviral drugs. In the first part of this review, we describe how viruses activate the IFN system, how IFNs induce transcription of their target genes and the mechanism of action of IFN-induced proteins with antiviral action. In the second part, we describe how viruses circumvent the IFN response. Here, we reflect upon possible consequences for both the virus and host of the different strategies that viruses have evolved and discuss whether certain viruses have exploited the IFN response to modulate their life cycle (e.g. to establish and maintain persistent/latent infections), whether perturbation of the IFN response by persistent infections can lead to chronic disease, and the importance of the IFN system as a species barrier to virus infections. Lastly, we briefly describe applied aspects that arise from an increase in our knowledge in this area, including vaccine design and manufacture, the development of novel antiviral drugs and the use of IFN-sensitive oncolytic viruses in the treatment of cancer.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Viruses
                Journal ID (iso-abbrev): Viruses
                Journal ID (publisher-id): viruses
                Title: Viruses
                Publisher: MDPI
                ISSN (Electronic): 1999-4915
                Publication date (Electronic): 28 February 2018
                Publication date Collection: March 2018
                Volume: 10
                Issue: 3
                Electronic Location Identifier: 101
                Affiliations
                Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK; jd732@ 123456cam.ac.uk (J.D.A.); at678@ 123456cam.ac.uk (A.A.T.)
                Author notes
                [* ]Correspondence: gls37@ 123456cam.ac.uk
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-8792-813X
                Article
                Publisher ID: viruses-10-00101
                DOI: 10.3390/v10030101
                PMC ID: 5869494
                PubMed ID: 29495547
                SO-VID: e2e2a06b-b733-40e0-8b7a-9d115ae25b5f
                Copyright © © 2018 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 07 February 2018
                Date accepted : 22 February 2018
                Categories
                Subject: Review

                ScienceOpen disciplines: Microbiology & Virology
                Keywords: vaccinia virus,vaccine,smallpox,immune evasion,genetic engineering,immunological memory,orthopoxviruses
                Data availability:
                ScienceOpen disciplines: Microbiology & Virology
                Keywords: vaccinia virus, vaccine, smallpox, immune evasion, genetic engineering, immunological memory, orthopoxviruses

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