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      From discovery to licensure, the Adjuvant System story

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          ABSTRACT

          Adjuvants are substances added to vaccines to improve their immunogenicity. Used for more than 80 years, aluminum, the first adjuvant in human vaccines, proved insufficient to develop vaccines that could protect against new challenging pathogens such as HIV and malaria. New adjuvants and new combinations of adjuvants (Adjuvant Systems) have opened the door to the delivery of improved and new vaccines against re-emerging and difficult pathogens. Adjuvant Systems concept started through serendipity. The access to new developments in technology, microbiology and immunology have been instrumental for the dicephering of what they do and how they do it. This knowledge opens the door to more rational vaccine design with implications for developing new and better vaccines.

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          Most cited references69

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          Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women

          The Lancet, 374(9686), 301-314
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            Innate immune sensing and its roots: the story of endotoxin.

            How does the host sense pathogens? Our present concepts grew directly from longstanding efforts to understand infectious disease: how microbes harm the host, what molecules are sensed and, ultimately, the nature of the receptors that the host uses. The discovery of the host sensors--the Toll-like receptors--was rooted in chemical, biological and genetic analyses that centred on a bacterial poison, termed endotoxin.
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              Understanding immunosenescence to improve responses to vaccines.

              In the older adult, the benefits of vaccination to prevent infectious disease are limited, mainly because of the adaptive immune system's inability to generate protective immunity. The age-dependent decrease in immunological competence, often referred to as 'immunosenescence', results from the progressive deterioration of innate and adaptive immune responses. Most insights into mechanisms of immunological aging have been derived from studies of mouse models. In this Review, we explore how well such models are applicable to understanding the aging process throughout the 80-100 years of human life and discuss recent advances in identifying and characterizing the mechanisms that underlie age-associated defective adaptive immunity in humans.
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                Author and article information

                Journal
                Hum Vaccin Immunother
                Hum Vaccin Immunother
                KHVI
                khvi20
                Human Vaccines & Immunotherapeutics
                Taylor & Francis
                2164-5515
                2164-554X
                January 2017
                16 September 2016
                16 September 2016
                : 13
                : 1
                : 19-33
                Affiliations
                [a ]Bioaster , Lyon, France
                [b ]GSK Vaccines , Wavre, Belgium
                Author notes
                CONTACT Alberta Di Pasquale ALBERTA.DI-PASQUALE@ 123456GSK.COM GSK Vaccines , Av Fleming 20, Parc de la Noire Epine, B-1300 Wavre, Belgium

                Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/khvi.

                Article
                1225635
                10.1080/21645515.2016.1225635
                5287309
                27636098
                053bf6d5-8920-4611-9387-b0b7728b110e
                © 2017 The Author(s). Published with license by Taylor & Francis.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.

                History
                : 2 May 2016
                : 28 July 2016
                : 13 August 2016
                Page count
                Figures: 4, Tables: 2, References: 104, Pages: 15
                Categories
                Reviews

                Molecular medicine
                adaptive immune response,adjuvanted vaccine,adjuvant,adjuvant system,innate immune response,vaccine development

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