A Single-dose Live-attenuated Vaccine Prevents Zika Virus Pregnancy Transmission and Testis Damage

Overview

Journal Nat Commun

Specialty Biology

Date 2017 Sep 24

PMID 28939807

Citations 93

Authors

Chao Shan

Antonio E Muruato

Brett W Jagger

Justin Richner

Bruno T D Nunes

Daniele B A Medeiros

Xuping Xie

Jannyce G C Nunes

Kaitlyn M Morabito

Wing-Pui Kong

Theodore C Pierson

Alan D Barrett

Scott C Weaver

Shannan L Rossi

Pedro F C Vasconcelos

Barney S Graham

Michael S Diamond

Pei-Yong Shi

Affiliations

Soon will be listed here.

Abstract

Zika virus infection during pregnancy can cause congenital abnormities or fetal demise. The persistence of Zika virus in the male reproductive system poses a risk of sexual transmission. Here we demonstrate that live-attenuated Zika virus vaccine candidates containing deletions in the 3' untranslated region of the Zika virus genome (ZIKV-3'UTR-LAV) prevent viral transmission during pregnancy and testis damage in mice, as well as infection of nonhuman primates. After a single-dose vaccination, pregnant mice challenged with Zika virus at embryonic day 6 and evaluated at embryonic day 13 show markedly diminished levels of viral RNA in maternal, placental, and fetal tissues. Vaccinated male mice challenged with Zika virus were protected against testis infection, injury, and oligospermia. A single immunization of rhesus macaques elicited a rapid and robust antibody response, conferring complete protection upon challenge. Furthermore, the ZIKV-3'UTR-LAV vaccine candidates have a desirable safety profile. These results suggest that further development of ZIKV-3'UTR-LAV is warranted for humans.Zika virus infection can result in congenital disorders and cause disease in adults, and there is currently no approved vaccine. Here Shan et al. show that a single dose of a live-attenuated Zika vaccine prevents infection, testis damage and transmission to the fetus during pregnancy in different animal models.

Citing Articles

Comparison of Three Chimeric Zika Vaccine Prototypes Developed on the Genetic Background of the Clinically Proven Live-Attenuated Japanese Encephalitis Vaccine SA-14-2.

Song B, Frank J, Yun S, Julander J, Mason J, Polejaeva I Int J Mol Sci. 2025; 26(1.

PMID: 39796052 PMC: 11720029. DOI: 10.3390/ijms26010195.

An Overview of Zika Virus and Zika Virus Induced Neuropathies.

Wahaab A, Mustafa B, Hameed M, Batool H, Tran Nguyen Minh H, Tawaab A Int J Mol Sci. 2025; 26(1.

PMID: 39795906 PMC: 11719530. DOI: 10.3390/ijms26010047.

Subgenomic flavivirus RNA as key target for live-attenuated vaccine development.

Doets K, Pijlman G J Virol. 2024; 98(7):e0010023.

PMID: 38808973 PMC: 11265276. DOI: 10.1128/jvi.00100-23.

A live attenuated vaccine to prevent severe neonatal Escherichia coli K1 infections.

Sereme Y, Schrimp C, Faury H, Agapoff M, Lefebvre-Wloszczowski E, Chang Marchand Y Nat Commun. 2024; 15(1):3021.

PMID: 38589401 PMC: 11001983. DOI: 10.1038/s41467-024-46775-x.

A review on Zika vaccine development.

Peng Z, Yang S, Lu H, Wang L, Li N, Zhang H Pathog Dis. 2024; 82.

PMID: 38192053 PMC: 10901608. DOI: 10.1093/femspd/ftad036.

References

Grant A, Ponia S, Tripathi S, Balasubramaniam V, Miorin L, Sourisseau M . Zika Virus Targets Human STAT2 to Inhibit Type I Interferon Signaling. Cell Host Microbe. 2016; 19(6):882-90. PMC: 4900918. DOI: 10.1016/j.chom.2016.05.009. View

Larocca R, Abbink P, Peron J, Zanotto P, Iampietro M, Badamchi-Zadeh A . Vaccine protection against Zika virus from Brazil. Nature. 2016; 536(7617):474-8. PMC: 5003703. DOI: 10.1038/nature18952. View

Abbink P, Larocca R, De La Barrera R, Bricault C, Moseley E, Boyd M . Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys. Science. 2016; 353(6304):1129-32. PMC: 5237380. DOI: 10.1126/science.aah6157. View

. Acceptability of cell substrates for production of biologicals. Report of a WHO Study Group on Biologicals. World Health Organ Tech Rep Ser. 1987; 747:1-29. View

Arsuaga M, Garcia Bujalance S, Diaz-Menendez M, Vazquez A, Arribas J . Probable sexual transmission of Zika virus from a vasectomised man. Lancet Infect Dis. 2016; 16(10):1107. DOI: 10.1016/S1473-3099(16)30320-6. View

Brasil P, Pereira Jr J, Moreira M, Ribeiro Nogueira R, Damasceno L, Wakimoto M . Zika Virus Infection in Pregnant Women in Rio de Janeiro. N Engl J Med. 2016; 375(24):2321-2334. PMC: 5323261. DOI: 10.1056/NEJMoa1602412. View

Richner J, Jagger B, Shan C, Fontes C, Dowd K, Cao B . Vaccine Mediated Protection Against Zika Virus-Induced Congenital Disease. Cell. 2017; 170(2):273-283.e12. PMC: 5546158. DOI: 10.1016/j.cell.2017.06.040. View

Russell K, Hills S, Oster A, Porse C, Danyluk G, Cone M . Male-to-Female Sexual Transmission of Zika Virus-United States, January-April 2016. Clin Infect Dis. 2016; 64(2):211-213. DOI: 10.1093/cid/ciw692. View

Uraki R, Hwang J, Jurado K, Householder S, Yockey L, Hastings A . Zika virus causes testicular atrophy. Sci Adv. 2017; 3(2):e1602899. PMC: 5321463. DOI: 10.1126/sciadv.1602899. View

10.

Fernandez E, Diamond M . Vaccination strategies against Zika virus. Curr Opin Virol. 2017; 23:59-67. PMC: 5576498. DOI: 10.1016/j.coviro.2017.03.006. View

11.

Shan C, Xie X, Ren P, Loeffelholz M, Yang Y, Furuya A . A Rapid Zika Diagnostic Assay to Measure Neutralizing Antibodies in Patients. EBioMedicine. 2017; 17:157-162. PMC: 5360589. DOI: 10.1016/j.ebiom.2017.03.006. View

12.

Richner J, Himansu S, Dowd K, Butler S, Salazar V, Fox J . Modified mRNA Vaccines Protect against Zika Virus Infection. Cell. 2017; 168(6):1114-1125.e10. PMC: 5388441. DOI: 10.1016/j.cell.2017.02.017. View

13.

Ma W, Li S, Ma S, Jia L, Zhang F, Zhang Y . Zika Virus Causes Testis Damage and Leads to Male Infertility in Mice. Cell. 2016; 167(6):1511-1524.e10. DOI: 10.1016/j.cell.2016.11.016. View

14.

Griffin B, Muthumani K, Warner B, Majer A, Hagan M, Audet J . DNA vaccination protects mice against Zika virus-induced damage to the testes. Nat Commun. 2017; 8:15743. PMC: 5467228. DOI: 10.1038/ncomms15743. View

15.

Lazear H, Govero J, Smith A, Platt D, Fernandez E, Miner J . A Mouse Model of Zika Virus Pathogenesis. Cell Host Microbe. 2016; 19(5):720-30. PMC: 4866885. DOI: 10.1016/j.chom.2016.03.010. View

16.

Xie X, Yang Y, Muruato A, Zou J, Shan C, Nunes B . Understanding Zika Virus Stability and Developing a Chimeric Vaccine through Functional Analysis. mBio. 2017; 8(1). PMC: 5296601. DOI: 10.1128/mBio.02134-16. View

17.

Guerbois M, Fernandez-Salas I, Azar S, Danis-Lozano R, Alpuche-Aranda C, Leal G . Outbreak of Zika Virus Infection, Chiapas State, Mexico, 2015, and First Confirmed Transmission by Aedes aegypti Mosquitoes in the Americas. J Infect Dis. 2016; 214(9):1349-1356. PMC: 5079363. DOI: 10.1093/infdis/jiw302. View

18.

Shan C, Xie X, Barrett A, Garcia-Blanco M, Tesh R, da Costa Vasconcelos P . Zika Virus: Diagnosis, Therapeutics, and Vaccine. ACS Infect Dis. 2016; 2(3):170-2. DOI: 10.1021/acsinfecdis.6b00030. View

19.

Barzon L, Pacenti M, Franchin E, Lavezzo E, Trevisan M, Sgarabotto D . Infection dynamics in a traveller with persistent shedding of Zika virus RNA in semen for six months after returning from Haiti to Italy, January 2016. Euro Surveill. 2016; 21(32). PMC: 4998504. DOI: 10.2807/1560-7917.ES.2016.21.32.30316. View

20.

Ong E, Budigi Y, Tan H, Robinson L, Rowley K, Winnett A . Preclinical evaluation of VIS513, a therapeutic antibody against dengue virus, in non-human primates. Antiviral Res. 2017; 144:44-47. DOI: 10.1016/j.antiviral.2017.05.007. View