Rapid development of a DNA vaccine for Zika virus

Dowd, Kimberly A.; Ko, Sung-Youl; Morabito, Kaitlyn M.; Yang, Eun Sung; Pelc, Rebecca S.; DeMaso, Christina R.; Castilho, Leda R.; Abbink, Peter; Boyd, Michael; Nityanandam, Ramya; Gordon, David; Gallagher, John R.; Chen, Xuejun; Todd, John-Paul M.; Tsybovsky, Yaroslav; Harris, Audray K.; Huang, Yan-Jang S.; Higgs, Stephen; Vanlandingham, Dana L.; Andersen, Hanné; Lewis, Mark G.; Barrera, Rafael De La; Eckels, Kenneth H.; Jarman, Richard G.; Nason, Martha; Barouch, Dan H.; Roederer, Mario; Kong, Wing-Pui; Mascola, John R.; Pierson, Theodore C.; Graham, Barney S.

doi:10.1126/science.aai9137

Cited by 351 publications

(358 citation statements)

References 31 publications

Supporting

Mentioning

334

Contrasting

Unclassified

Order By: Relevance

“…These encompass the use of established approaches, such as purified inactivated virus (PIV) (20,21), to more advanced approaches, such as DNA (prM-E) (20)(21)(22), subunit (E) (23), and recombinant adenovirus (20,23) platforms, along with the recent development of RNA nanoparticle technology (24) or modified mRNA (prM-E) (25,26), as vaccine candidates. Studies have demonstrated an effective neutralizing antibody response capable of protecting against ZIKV infection in both mice and nonhuman primates (20)(21)(22), leading to several clinical trials that are under way (ClinicalTrials.gov identifiers NCT02963909, NCT02840487, NCT02887482, NCT02809443, and NCT02952833). While virus-like particle (VLP)-based vaccines have been tested for nearly all flaviviruses, a VLP-based approach for ZIKV was only recently described (27) and needs further testing.…”

mentioning

confidence: 99%

Development of Virus-Like-Particle Vaccine and Reporter Assay for Zika Virus

Garg

Sedano

Plata

et al. 2017

J Virol

View full text Add to dashboard Cite

Recent worldwide outbreaks of Zika virus (ZIKV) infection and the lack of an approved vaccine raise serious concerns regarding preparedness to combat this emerging virus. We used a virus-like particle (VLP)-based approach to develop a vaccine and a microneutralization assay for ZIKV. A synthetic capsid-premembrane-envelope (CprM-E) gene construct of ZIKV was used to generate reporter virus particles (RVPs) that package a green fluorescent protein (GFP) reporter-expressing West Nile virus (WNV) replicon. The assay was adapted to a 96-well format, similar to the plaque reduction neutralization test (PRNT), and showed high reproducibility with specific detection of ZIKV neutralizing antibodies. Furthermore, C-prM-E and prM-E VLPs were tested as vaccine candidates in mice and compared to DNA vaccination. While the ZIKV prM-E construct alone was sufficient for generating VLPs, efficient VLP production from the C-prM-E construct could be achieved in the presence of the WNV NS2B-3 protease, which cleaves C from prM, allowing virus release. Immunization studies in mice showed that VLPs generated higher neutralizing antibody titers than those with the DNA vaccines, with C-prM-E VLPs giving slightly higher titers than those with prM-E VLPs. The superiority of C-prM-E VLPs suggests that inclusion of capsid may have benefits for ZIKV and other flaviviral VLP vaccines. To facilitate the VLP platform, we generated a stable cell line expressing high levels of ZIKV prM-E proteins that constitutively produce VLPs as well as a cell line expressing ZIKV C-prM-E proteins for RVP production. While several vaccine platforms have been proposed for ZIKV, this study describes a safe, effective, and economical VLP-based vaccine against ZIKV.IMPORTANCE To address the growing Zika virus epidemic, we undertook this study with two objectives: first, to develop a safe, effective, and economical vaccine for ZIKV, and second, to develop a rapid and versatile assay to detect the anti-ZIKV immune response. We generated a cell line stably expressing ZIKV prM-E that produces large amounts of VLPs in the supernatant and a ZIKV C-prM-E cell line that produces reporter virus particles upon transfection with a GFP replicon plasmid. The prM-E VLPs induced a strong neutralizing antibody response in mice that was better when the capsid was included. VLP-based vaccines showed significantly better neutralizing antibody responses than those with their DNA counterparts. The RVP-based microneutralization assay worked similarly to the PRNT assay, with a rapid GFP readout in a 96-well format. Our VLP-based platform provides a source for a ZIKV vaccine and diagnosis that can rapidly be adapted to current outbreaks.KEYWORDS C-prM-E, diagnostics, microneutralization, neutralization, PRNT, reporter, reporter virus particles, vaccine, Zika, prM-E S ince the identification of Zika virus (ZIKV) from a rhesus monkey in Uganda in 1947 (1, 2) until 2010, the virus predominantly circulated between Aedes mosquitoes and nonhuman primates. Periodic episodes were inde...

show abstract

mentioning

confidence: 99%

Development of Virus-Like-Particle Vaccine and Reporter Assay for Zika Virus

Garg

Sedano

Plata

et al. 2017

J Virol

View full text Add to dashboard Cite

show abstract

“…Preclinical studies demonstrated that both vaccines induced high neutralising antibody titers and completely protected animals against ZIKV challenges [67,68,75].…”

Section: Inactivatedmentioning

confidence: 99%

“…Recombinant protein, DNA and RNA Two DNA based vaccines expressing the ZIKV proteins prM and E are currently tested in healthy volunteers [67,75]. Preclinical studies demonstrated that both vaccines induced high neutralising antibody titers and completely protected animals against ZIKV challenges [67,68,75].…”

Section: Inactivatedmentioning

confidence: 99%

Recent advances in human flavivirus vaccines

Scherwitzl

Mongkolsapaja

Screaton

2017

Current Opinion in Virology

View full text Add to dashboard Cite

“…The recent example that emphasizes this benefit is Zika virus epidemic. A clinical case report [5,6] can lead to subsequent analytic studies to characterize clinical manifestations, investigations, transmission, and complications of Zika virus infection in human and further studies during Zika virus outbreak [7][8][9][10][11][12][13] as well as discovery of management and prevention such as vaccine [14,15].…”

Section: Editorial Open Accessmentioning

confidence: 99%

Case reports and case series versus modern evidence-based medicine: Merit for an individual patient and public health

Tantisattamo¹

2017

IJCRI

View full text Add to dashboard Cite

International Journal of Case Reports and Images (IJCRI) is an international, peer reviewed, monthly, open access, online journal, publishing high-quality, articles in all areas of basic medical sciences and clinical specialties.Aim of IJCRI is to encourage the publication of new information by providing a platform for reporting of unique, unusual and rare cases which enhance understanding of disease process, its diagnosis, management and clinico-pathologic correlations. IJCRI publishes Review

show abstract

Rapid development of a DNA vaccine for Zika virus

Cited by 351 publications

References 31 publications

Development of Virus-Like-Particle Vaccine and Reporter Assay for Zika Virus

Development of Virus-Like-Particle Vaccine and Reporter Assay for Zika Virus

Recent advances in human flavivirus vaccines

Case reports and case series versus modern evidence-based medicine: Merit for an individual patient and public health

Contact Info

Product

Resources

About