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      Population implications of the deployment of novel universal vaccines against epidemic and pandemic influenza

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          Abstract

          There is increasing interest in the development of new, ‘universal’ influenza vaccines (UIVs) that––unlike current vaccines––are effective against a broad range of seasonal influenza strains, as well as against novel pandemic viruses. While the existing literature discusses the potential epidemiological benefits of UIVs, it is also important to anticipate their potential unintended population consequences. Using mathematical modelling, we illustrate two such types of adverse consequences. First, by reducing the amount of infection-induced immunity in a population without fully replacing it, a seasonal UIV programme may permit larger pandemics than in the absence of vaccination. Second, the more successful a future UIV programme is in reducing transmission of seasonal influenza, the more vulnerable the population could become to the emergence of a vaccine escape variant. These risks could be mitigated by optimal deployment of any future UIV vaccine: namely, the use of a combined vaccine formulation (incorporating conventional as well as multiple universal antigenic targets) and achieving sufficient population coverage to compensate for any reductions in infection-induced immunity. In the absence of large-scale trials of UIVs, disease-dynamic models can provide helpful, early insights into their potential impact. In future, data from continuing vaccine development will be invaluable in developing robustly predictive modelling approaches.

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          Most cited references17

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          Influenza virus hemagglutinin stalk-based antibodies and vaccines.

          Antibodies against the conserved stalk domain of the hemagglutinin are currently being discussed as promising therapeutic tools against influenza virus infections. Because of the conservation of the stalk domain these antibodies are able to broadly neutralize a wide spectrum of influenza virus strains and subtypes. Broadly protective vaccine candidates based on the epitopes of these antibodies, for example, chimeric and headless hemagglutinin structures, are currently under development and show promising results in animals models. These candidates could be developed into universal influenza virus vaccines that protect from infection with drifted seasonal as well as novel pandemic influenza virus strains therefore obviating the need for annual vaccination, and enhancing our pandemic preparedness. Copyright © 2013 Elsevier B.V. All rights reserved.
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            From Original Antigenic Sin to the Universal Influenza Virus Vaccine.

            Antibody responses are essential for protection against influenza virus infection. Humans are exposed to a multitude of influenza viruses throughout their lifetime and it is clear that immune history influences the magnitude and quality of the antibody response. The 'original antigenic sin' concept refers to the impact of the first influenza virus variant encounter on lifelong immunity. Although this model has been challenged since its discovery, past exposure, and likely one's first exposure, clearly affects the epitopes targeted in subsequent responses. Understanding how previous exposure to influenza virus shapes antibody responses to vaccination and infection is critical, especially with the prospect of future pandemics and for the effective development of a universal influenza vaccine.
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              Hemagglutinin stalk-based universal vaccine constructs protect against group 2 influenza A viruses.

              Current influenza virus vaccines contain H1N1 (phylogenetic group 1 hemagglutinin), H3N2 (phylogenetic group 2 hemagglutinin), and influenza B virus components. These vaccines induce good protection against closely matched strains by predominantly eliciting antibodies against the membrane distal globular head domain of their respective viral hemagglutinins. This domain, however, undergoes rapid antigenic drift, allowing the virus to escape neutralizing antibody responses. The membrane proximal stalk domain of the hemagglutinin is much more conserved compared to the head domain. In recent years, a growing collection of antibodies that neutralize a broad range of influenza virus strains and subtypes by binding to this domain has been isolated. Here, we demonstrate that a vaccination strategy based on the stalk domain of the H3 hemagglutinin (group 2) induces in mice broadly neutralizing anti-stalk antibodies that are highly cross-reactive to heterologous H3, H10, H14, H15, and H7 (derived from the novel Chinese H7N9 virus) hemagglutinins. Furthermore, we demonstrate that these antibodies confer broad protection against influenza viruses expressing various group 2 hemagglutinins, including an H7 subtype. Through passive transfer experiments, we show that the protection is mediated mainly by neutralizing antibodies against the stalk domain. Our data suggest that, in mice, a vaccine strategy based on the hemagglutinin stalk domain can protect against viruses expressing divergent group 2 hemagglutinins.
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                Author and article information

                Journal
                J R Soc Interface
                J R Soc Interface
                RSIF
                royinterface
                Journal of the Royal Society Interface
                The Royal Society
                1742-5689
                1742-5662
                March 2020
                4 March 2020
                4 March 2020
                : 17
                : 164
                : 20190879
                Affiliations
                [1 ]MRC Centre for Global Infectious Disease Analysis, Faculty of Medicine, Imperial College London, London , UK
                [2 ]Department of Infectious Disease, Faculty of Medicine, Imperial College London, London , UK
                [3 ]Lewis-Sigler Institute for Integrative Genomics, Princeton University , Princeton, NJ, USA
                [4 ]Department of Ecology and Evolutionary Biology, Princeton University , Princeton, NJ, USA
                Author notes

                Electronic supplementary material is available online at https://doi.org/10.6084/m9.figshare.c.4862262.

                Author information
                http://orcid.org/0000-0001-9502-6876
                Article
                rsif20190879
                10.1098/rsif.2019.0879
                7115234
                32126190
                934dc3fb-d87a-47b5-bedc-498dfdfb027b
                © 2020 The Author(s)

                Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.

                History
                : 22 December 2019
                : 12 February 2020
                Funding
                Funded by: Medical Research Council, http://dx.doi.org/10.13039/501100000265;
                Award ID: MR/R015600/1
                Categories
                1004
                24
                44
                Life Sciences–Mathematics interface
                Report
                Custom metadata
                March 4, 2020

                Life sciences
                influenza,epidemiology,mathematical modelling,vaccine
                Life sciences
                influenza, epidemiology, mathematical modelling, vaccine

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