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      Vector-based genetically modified vaccines: Exploiting Jenner’s legacy

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          Abstract

          The global vaccine market is diverse while facing a plethora of novel developments. Genetic modification (GM) techniques facilitate the design of ’smarter’ vaccines. For many of the major infectious diseases of humans, like AIDS and malaria, but also for most human neoplastic disorders, still no vaccines are available. It may be speculated that novel GM technologies will significantly contribute to their development. While a promising number of studies is conducted on GM vaccines and GM vaccine technologies, the contribution of GM technology to newly introduced vaccines on the market is disappointingly limited.

          In this study, the field of vector-based GM vaccines is explored. Data on currently available, actually applied, and newly developed vectors is retrieved from various sources, synthesised and analysed, in order to provide an overview on the use of vector-based technology in the field of GM vaccine development. While still there are only two vector-based vaccines on the human vaccine market, there is ample activity in the fields of patenting, preclinical research, and different stages of clinical research. Results of this study revealed that vector-based vaccines comprise a significant part of all GM vaccines in the pipeline. This study further highlights that poxviruses and adenoviruses are among the most prominent vectors in GM vaccine development.

          After the approval of the first vectored human vaccine, based on a flavivirus vector, vaccine vector technology, especially based on poxviruses and adenoviruses, holds great promise for future vaccine development. It may lead to cheaper methods for the production of safe vaccines against diseases for which no or less perfect vaccines exist today, thus catering for an unmet medical need. After the introduction of Jenner’s vaccinia virus as the first vaccine more than two centuries ago, which eventually led to the recent eradication of smallpox, this and other viruses may now be the basis for constructing vectors that may help us control other major scourges of mankind.

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          Most cited references40

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          Adenoviruses as vaccine vectors

          Adenoviruses have transitioned from tools for gene replacement therapy to bona fide vaccine delivery vehicles. They are attractive vaccine vectors as they induce both innate and adaptive immune responses in mammalian hosts. Currently, adenovirus vectors are being tested as subunit vaccine systems for numerous infectious agents ranging from malaria to HIV-1. Additionally, they are being explored as vaccines against a multitude of tumor-associated antigens. In this review we describe the molecular biology of adenoviruses as well as ways the adenovirus vectors can be manipulated to enhance their efficacy as vaccine carriers. We describe methods of evaluating immune responses to transgene products expressed by adenoviral vectors and discuss data on adenoviral vaccines to a selected number of pathogens. Last, we comment on the limitations of using human adenoviral vectors and provide alternatives to circumvent these problems. This field is growing at an exciting and rapid pace, thus we have limited our scope to the use of adenoviral vectors as vaccines against viral pathogens.
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            Hepatitis B vaccines.

            (2009)
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              Is Open Access

              Pre-existing immunity against vaccine vectors – friend or foe?

              Over the last century, the successful attenuation of multiple bacterial and viral pathogens has led to an effective, robust and safe form of vaccination. Recently, these vaccines have been evaluated as delivery vectors for heterologous antigens, as a means of simultaneous vaccination against two pathogens. The general consensus from published studies is that these vaccine vectors have the potential to be both safe and efficacious. However, some of the commonly employed vectors, for example Salmonella and adenovirus, often have pre-existing immune responses in the host and this has the potential to modify the subsequent immune response to a vectored antigen. This review examines the literature on this topic, and concludes that for bacterial vectors there can in fact, in some cases, be an enhancement in immunogenicity, typically humoral, while for viral vectors pre-existing immunity is a hindrance for subsequent induction of cell-mediated responses.
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                Author and article information

                Contributors
                Journal
                Vaccine
                Vaccine
                Vaccine
                The Author(s). Published by Elsevier Ltd.
                0264-410X
                1873-2518
                28 October 2016
                7 December 2016
                28 October 2016
                : 34
                : 50
                : 6436-6448
                Affiliations
                [a ]Vrije Universiteit Amsterdam, Earth & Life Sciences, Athena Institute, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands
                [b ]University of Veterinary Medicine Hannover, Foundation, Bünteweg 17, 30559 Hannover, Germany
                Author notes
                [* ]Corresponding author. a.osterhaus@ 123456hotmail.com
                Article
                S0264-410X(16)30510-2
                10.1016/j.vaccine.2016.06.059
                7115478
                28029542
                55fe609f-5e52-4fcc-9ced-90478f4f60a5
                © 2016 The Author(s)

                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
                : 11 February 2016
                : 2 June 2016
                : 20 June 2016
                Categories
                Article

                Infectious disease & Microbiology
                genetically modified techniques,genetically modifies vaccines,novel vaccine platforms,vector-based vaccines,vectors,poxviruses and adenoviruses

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