A single-dose live attenuated chimeric vaccine candidate against Zika virus
Wei-Xin Chin,
Regina Ching Hua Lee,
Parveen Kaur,
Tian Sheng Lew,
Thinesshwary Yogarajah,
Hao Yuin Kong,
Zi-Yun Teo,
Cyrill Kafi Salim,
Rong-Rong Zhang,
Xiao-Feng Li,
Sylvie Alonso,
Cheng-Feng Qin,
Justin Jang Hann Chu
Affiliations
Wei-Xin Chin
Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore
Regina Ching Hua Lee
Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore
Parveen Kaur
Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore
Tian Sheng Lew
Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore
Thinesshwary Yogarajah
Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore
Hao Yuin Kong
NUSMed Biosafety Level 3 Core Facility, Yong Loo Lin School of Medicine, National University of Singapore
Zi-Yun Teo
Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore
Cyrill Kafi Salim
Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore
Rong-Rong Zhang
Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology
Xiao-Feng Li
Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology
Sylvie Alonso
Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine
Cheng-Feng Qin
Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology
Justin Jang Hann Chu
Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore
Abstract The mosquito-borne Zika virus is an emerging pathogen from the Flavivirus genus for which there are no approved antivirals or vaccines. Using the clinically validated PDK-53 dengue virus vaccine strain as a backbone, we created a chimeric dengue/Zika virus, VacDZ, as a live attenuated vaccine candidate against Zika virus. VacDZ demonstrates key markers of attenuation: small plaque phenotype, temperature sensitivity, attenuation of neurovirulence in suckling mice, and attenuation of pathogenicity in interferon deficient adult AG129 mice. VacDZ may be administered as a traditional live virus vaccine, or as a DNA-launched vaccine that produces live VacDZ in vivo after delivery. Both vaccine formulations induce a protective immune response against Zika virus in AG129 mice, which includes neutralising antibodies and a strong Th1 response. This study demonstrates that VacDZ is a safe and effective vaccine candidate against Zika virus.
