Development of a chimeric Zika vaccine using a licensed live-attenuated flavivirus vaccine as backbone

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

The global spread of Zika virus (ZIKV) and its unexpected association with congenital defects necessitates the rapid development of a safe and effective vaccine. Here we report the development and characterization of a recombinant chimeric ZIKV vaccine candidate (termed ChinZIKV) that expresses the prM-E proteins of ZIKV using the licensed Japanese encephalitis live-attenuated vaccine SA14-14-2 as the genetic backbone. ChinZIKV retains its replication activity and genetic stability in vitro, while exhibiting an attenuation phenotype in multiple animal models. Remarkably, immunization of mice and rhesus macaques with a single dose of ChinZIKV elicits robust and long-lasting immune responses, and confers complete protection against ZIKV challenge. Significantly, female mice immunized with ChinZIKV are protected against placental and fetal damage upon ZIKV challenge during pregnancy. Overall, our study provides an alternative vaccine platform in response to the ZIKV emergency, and the safety, immunogenicity, and protection profiles of ChinZIKV warrant further clinical development.

Abstract

Given the recent Zika virus (ZIKV) epidemic, development of an effective vaccine is of high importance. Here, the authors use a licensed live-attenuated flavivirus vaccine backbone to develop a ZIKV vaccine and determine immunogenicity, safety and protection profiles in different animal models.

Related collections

Most cited references 35

Record: found
Abstract: found
Article: not found

Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys.

P Abbink, R. A. Larocca, R. A. De La Barrera … (2016)

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.

0 comments Cited 242 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Rapid development of a DNA vaccine for Zika virus.

Kimberly Dowd, Sung-Youl Ko, Kaitlyn Morabito … (2016)

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.

0 comments Cited 185 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

CCR5 deficiency increases risk of symptomatic West Nile virus infection

William G. Glass, David McDermott, Jean Lim … (2006)

West Nile virus (WNV) is a reemerging pathogen that causes fatal encephalitis in several species, including mouse and human. Recently, we showed that the chemokine receptor CCR5 is critical for survival of mice infected with WNV, acting at the level of leukocyte trafficking to the brain. To test whether this receptor is also protective in man, we determined the frequency of CCR5Δ32, a defective CCR5 allele found predominantly in Caucasians, in two independent cohorts of patients, one from Arizona and the other from Colorado, who had laboratory-confirmed, symptomatic WNV infection. The distribution of CCR5Δ32 in a control population of healthy United States Caucasian random blood donors was in Hardy-Weinberg equilibrium and CCR5Δ32 homozygotes represented 1.0% of the total group (n = 1,318). In contrast, CCR5Δ32 homozygotes represented 4.2% of Caucasians in the Arizona cohort (odds ratios [OR] = 4.4 [95% confidence interval [CI], 1.6–11.8], P = 0.0013) and 8.3% of Caucasians in the Colorado cohort (OR = 9.1 [95% CI, 3.4–24.8], P < 0.0001). CCR5Δ32 homozygosity was significantly associated with fatal outcome in the Arizona cohort (OR = 13.2 [95% CI, 1.9–89.9], P = 0.03). We conclude that CCR5 mediates resistance to symptomatic WNV infection. Because CCR5 is also the major HIV coreceptor, these findings have important implications for the safety of CCR5-blocking agents under development for HIV/AIDS.

0 comments Cited 145 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Cheng-Feng Qin:

ORCID: http://orcid.org/0000-0002-0632-2807

qincf@bmi.ac.cn

Journal

Journal ID (nlm-ta): Nat Commun

Journal ID (iso-abbrev): Nat Commun

Title: Nature Communications

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2041-1723

Publication date (Electronic): 14 February 2018

Publication date PMC-release: 14 February 2018

Publication date Collection: 2018

Volume: 9

Electronic Location Identifier: 673

Affiliations

[1 ]ISNI 0000 0004 1803 4911, GRID grid.410740.6, State Key Laboratory of Pathogen and Biosecurity, , Beijing Institute of Microbiology and Epidemiology, ; Beijing, 100071 China

[2 ]ISNI 0000 0000 8653 1072, GRID grid.410737.6, Guangzhou Eighth People’s Hospital, , Guangzhou Medical University, ; Guangzhou, 510060 China

[3 ]Department of Infection Control, The 306th Hospital of PLA, Beijing, 100101 China

[4 ]ISNI 0000 0004 1803 4911, GRID grid.410740.6, Laboratory Animal Center, , Academy of Military Medical Science, ; Beijing, 100071 China

[5 ]ISNI 0000 0000 9889 6335, GRID grid.413106.1, Center for Systems Medicine, Institute of Basic Medical Sciences, , Chinese Academy of Medical Sciences and Peking Union Medical College, ; Beijing, 100005 China

[6 ]ISNI 0000 0001 0662 3178, GRID grid.12527.33, Tsinghua-Peking Center for Life Sciences, School of Medicine, , Tsinghua University, ; Beijing, 100084 China

[7 ]ISNI 0000 0004 1936 7603, GRID grid.5337.2, Faculty of Biomedical Sciences, School of Cellular and Molecular Medicine, , University of Bristol, ; University Walk, Bristol, BS8 1TD UK

[8 ]ISNI 0000 0001 1547 9964, GRID grid.176731.5, Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, , University of Texas Medical Branch, ; Galveston, Texas 77555 USA

[9 ]ISNI 0000 0001 1547 9964, GRID grid.176731.5, Department of Pharmacology and Toxicology, , University of Texas Medical Branch, ; Galveston, Texas 77555 USA

Author information

Ya-Jun Song http://orcid.org/0000-0002-6628-2747

Cheng-Feng Qin http://orcid.org/0000-0002-0632-2807

Article

Publisher ID: 2975

DOI: 10.1038/s41467-018-02975-w

PMC ID: 5813210

PubMed ID: 29445153

SO-VID: d265dc13-7735-496d-ace3-dd5ae63db594

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 28 September 2017

Date accepted : 10 January 2018

Custom metadata

ScienceOpen disciplines: Uncategorized

Data availability:

ScienceOpen disciplines: Uncategorized

Comments

Comment on this article

scite_

Cited by 40

See all cited by

Most referenced authors 2,083

See all reference authors

Development of a chimeric Zika vaccine using a licensed live-attenuated flavivirus vaccine as backbone

Read this article at

Abstract

Abstract

Related collections

Zika Virus

Most cited references 35

Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys.

Rapid development of a DNA vaccine for Zika virus.

CCR5 deficiency increases risk of symptomatic West Nile virus infection

Author and article information

Contributors

Journal

Affiliations

Author information

Article

History

Categories

Custom metadata

Comments

Comment on this article

Similar content 366

Cited by 40

Most referenced authors 2,083