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      Zika Vaccine Development: Current Status

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          Abstract

          Zika virus outbreaks have been explosive and unpredictable and have led to significant adverse health effects—as well as considerable public anxiety. Significant scientific work has resulted in multiple candidate vaccines that are now undergoing further clinical development, with several vaccines now in phase 2 clinical trials. In this review, we survey current vaccine efforts, preclinical and clinical results, and ethical and other concerns that directly bear on vaccine development. It is clear that the world needs safe and effective vaccines to protect against Zika virus infection. Whether such vaccines can be developed through to licensure and public availability absent significant financial investment by countries, and other barriers discussed within this article, remains uncertain.

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          Most cited references45

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          Human antibody responses after dengue virus infection are highly cross-reactive to Zika virus.

          Zika virus (ZIKV) is an emerging mosquito-borne flavivirus of significant public health concern. ZIKV shares a high degree of sequence and structural homology compared with other flaviviruses, including dengue virus (DENV), resulting in immunological cross-reactivity. Improving our current understanding of the extent and characteristics of this immunological cross-reactivity is important, as ZIKV is presently circulating in areas that are highly endemic for dengue. To assess the magnitude and functional quality of cross-reactive immune responses between these closely related viruses, we tested acute and convalescent sera from nine Thai patients with PCR-confirmed DENV infection against ZIKV. All of the sera tested were cross-reactive with ZIKV, both in binding and in neutralization. To deconstruct the observed serum cross-reactivity in depth, we also characterized a panel of DENV-specific plasmablast-derived monoclonal antibodies (mAbs) for activity against ZIKV. Nearly half of the 47 DENV-reactive mAbs studied bound to both whole ZIKV virion and ZIKV lysate, of which a subset also neutralized ZIKV. In addition, both sera and mAbs from the dengue-infected patients enhanced ZIKV infection of Fc gamma receptor (FcγR)-bearing cells in vitro. Taken together, these findings suggest that preexisting immunity to DENV may impact protective immune responses against ZIKV. In addition, the extensive cross-reactivity may have implications for ZIKV virulence and disease severity in DENV-experienced populations.
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            Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys.

            Zika virus (ZIKV) is responsible for a major ongoing epidemic in the Americas and has been causally associated with fetal microcephaly. The development of a safe and effective ZIKV vaccine is therefore an urgent global health priority. Here we demonstrate that three different vaccine platforms protect against ZIKV challenge in rhesus monkeys. A purified inactivated virus vaccine induced ZIKV-specific neutralizing antibodies and completely protected monkeys against ZIKV strains from both Brazil and Puerto Rico. Purified immunoglobulin from vaccinated monkeys also conferred passive protection in adoptive transfer studies. A plasmid DNA vaccine and a single-shot recombinant rhesus adenovirus serotype 52 vector vaccine, both expressing ZIKV premembrane and envelope, also elicited neutralizing antibodies and completely protected monkeys against ZIKV challenge. These data support the rapid clinical development of ZIKV vaccines for humans.
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              Rapid development of a DNA vaccine for Zika virus.

              Zika virus (ZIKV) was identified as a cause of congenital disease during the explosive outbreak in the Americas and Caribbean that began in 2015. Because of the ongoing fetal risk from endemic disease and travel-related exposures, a vaccine to prevent viremia in women of childbearing age and their partners is imperative. We found that vaccination with DNA expressing the premembrane and envelope proteins of ZIKV was immunogenic in mice and nonhuman primates, and protection against viremia after ZIKV challenge correlated with serum neutralizing activity. These data not only indicate that DNA vaccination could be a successful approach to protect against ZIKV infection, but also suggest a protective threshold of vaccine-induced neutralizing activity that prevents viremia after acute infection.
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                Author and article information

                Contributors
                Journal
                Mayo Clin Proc
                Mayo Clin. Proc
                Mayo Clinic Proceedings
                Mayo Foundation
                0025-6196
                1942-5546
                2 December 2019
                December 2019
                2 December 2019
                : 94
                : 12
                : 2572-2586
                Affiliations
                [1]Mayo Clinic Vaccine Research Group, Division of General Internal Medicine, Mayo Clinic, Rochester, MN
                Author notes
                [] Correspondence: Address to Gregory A. Poland, MD, Director, Mayo Clinic Vaccine Research Group, Mayo Clinic, 200 First St SW, Rochester, MN 55905. poland.gregory@ 123456mayo.edu
                Article
                S0025-6196(19)30483-5
                10.1016/j.mayocp.2019.05.016
                7094556
                31806107
                4d798e89-77b3-4caa-bb05-e8fba7add1fe
                © 2019 Mayo Foundation for Medical Education and Research.

                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.

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                Article

                ade, antibody-dependent enhancement,c, capsid,denv, dengue virus,e, envelope,gbs, guillain-barré syndrome,ifn, interferon,irf, ifn response factor,mrna, messenger rna,prm, premembrane/membrane,who, world health organization,zikv, zika virus

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