A systematic approach to the development of a safe live attenuated Zika vaccine

Swee Sen Kwek; Satoru Watanabe; Kuan Rong Chan; Eugenia Z Ong; Hwee Cheng Tan; Wy Ching Ng; Mien T X Nguyen; Esther S Gan; Summer L Zhang; Kitti W K Chan; Jun Hao Tan; October M Sessions; Menchie Manuel; Julien Pompon; Camillus Chua; Sharifah Hazirah; Karl Tryggvason; Subhash G Vasudevan; Eng Eong Ooi

doi:10.1038/s41467-018-03337-2

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A systematic approach to the development of a safe live attenuated Zika vaccine

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A systematic approach to the development of a safe live attenuated Zika vaccine

Swee Sen Kwek, Satoru Watanabe, Kuan Rong Chan, Eugenia Z Ong, Hwee Cheng Tan, Wy Ching Ng, Mien T X Nguyen, Esther S Gan, Summer L Zhang, Kitti W K Chan, …

Nature communications, Vol.9(1), pp.1031-13

12/03/2018

DOI: https://doi.org/10.1038/s41467-018-03337-2

PMID: 29531213

Résumé

Aedes - immunology

Aedes - virology

Animals

Dendritic Cells - immunology

Dendritic Cells - virology

Humans

Immunologic Techniques

Mice

Vaccines, Attenuated - administration & dosage

Vaccines, Attenuated - genetics

Vaccines, Attenuated - immunology

Viral Vaccines - administration & dosage

Viral Vaccines - genetics

Viral Vaccines - immunology

Zika Virus - genetics

Zika Virus - growth & development

Zika Virus - immunology

Zika Virus Infection - immunology

Zika Virus Infection - prevention & control

Zika Virus Infection - virology

Zika virus (ZIKV) is a flavivirus that can cause congenital disease and requires development of an effective long-term preventative strategy. A replicative ZIKV vaccine with properties similar to the yellow fever 17D (YF17D) live-attenuated vaccine (LAV) would be advantageous, as a single dose of YF17D produces lifelong immunity. However, a replicative ZIKV vaccine must also be safe from causing persistent organ infections. Here we report an approach to ZIKV LAV development. We identify a ZIKV variant that produces small plaques due to interferon (IFN)-restricted viral propagation and displays attenuated infection of endothelial cells. We show that these properties collectively reduce the risk of organ infections and vertical transmission in a mouse model but remain sufficiently immunogenic to prevent wild-type ZIKV infection. Our findings suggest a strategy for the development of a safe but efficacious ZIKV LAV.

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Titre: A systematic approach to the development of a safe live attenuated Zika vaccine
Créateurs - sans rôle: Swee Sen Kwek - Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, 169857, Singapore
Satoru Watanabe - Duke-NUS Medical School
Kuan Rong Chan - Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, 169857, Singapore
Eugenia Z Ong - Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, 169857, Singapore
Hwee Cheng Tan - Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, 169857, Singapore
Wy Ching Ng - Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, 169857, Singapore
Mien T X Nguyen - Programme in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore, 169857, Singapore
Esther S Gan - Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, 169857, Singapore
Summer L Zhang - Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, 169857, Singapore
Kitti W K Chan - Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore
Jun Hao Tan - Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, 169857, Singapore
October M Sessions - Duke-NUS Medical School
Menchie Manuel - Duke-NUS Medical School
Julien Pompon - MIVEGEC, IRD, CNRS, Univ. Montpellier, 34394, Montpellier, France
Camillus Chua - SingHealth Translational Immunology and Inflammation Centre, SingHealth, Singapore, 169856, Singapore
Sharifah Hazirah - SingHealth Translational Immunology and Inflammation Centre, SingHealth, Singapore, 169856, Singapore
Karl Tryggvason - Department of Medical Biochemistry and Biophysics, Division of Matrix Biology, Karolinska Institute, 17177, Stockholm, Sweden
Subhash G Vasudevan - Duke-NUS Medical School
Eng Eong Ooi - Singapore-MIT Alliance for Research and Technology
Détails de publication: Nature communications, Vol.9(1), pp.1031-13
Identifiants: 99147830209311
Unité académique: Maladies Infectieuses et Vecteurs : Ecologie, Génétique, Evolution et Contrôle - MIVEGEC
Langue: English
Type de ressource: Journal article