A DNA Vaccine Protects Human Immune Cells Against Zika Virus Infection in Humanized Mice

Overview

Journal EBioMedicine

Specialty Biomedical Engineering

Date 2017 Oct 17

PMID 29033368

Citations 18

Authors

Guohua Yi

Xuequn Xu

Sojan Abraham

Sean Petersen

Hua Guo

Nora Ortega

Premlata Shankar

N Manjunath

Affiliations

Soon will be listed here.

Abstract

A DNA vaccine encoding prM and E protein has been shown to induce protection against Zika virus (ZIKV) infection in mice and monkeys. However, its effectiveness in humans remains undefined. Moreover, identification of which immune cell types are specifically infected in humans is unclear. We show that human myeloid cells and B cells are primary targets of ZIKV in humanized mice. We also show that a DNA vaccine encoding full length prM and E protein protects humanized mice from ZIKV infection. Following administration of the DNA vaccine, humanized DRAG mice developed antibodies targeting ZIKV as measured by ELISA and neutralization assays. Moreover, following ZIKV challenge, vaccinated animals presented virtually no detectable virus in human cells and in serum, whereas unvaccinated animals displayed robust infection, as measured by qRT-PCR. Our results utilizing humanized mice show potential efficacy for a targeted DNA vaccine against ZIKV in humans.

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References

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

DICK G, KITCHEN S, HADDOW A . Zika virus. I. Isolations and serological specificity. Trans R Soc Trop Med Hyg. 1952; 46(5):509-20. DOI: 10.1016/0035-9203(52)90042-4. View

Tabata T, Petitt M, Puerta-Guardo H, Michlmayr D, Wang C, Fang-Hoover J . Zika Virus Targets Different Primary Human Placental Cells, Suggesting Two Routes for Vertical Transmission. Cell Host Microbe. 2016; 20(2):155-66. PMC: 5257282. DOI: 10.1016/j.chom.2016.07.002. View

Kublin J, Whitney J . Zika virus research models. Virus Res. 2017; 254:15-20. PMC: 5809325. DOI: 10.1016/j.virusres.2017.07.025. View

Allam A, Majji S, Peachman K, Jagodzinski L, Kim J, Ratto-Kim S . TFH cells accumulate in mucosal tissues of humanized-DRAG mice and are highly permissive to HIV-1. Sci Rep. 2015; 5:10443. PMC: 4451806. DOI: 10.1038/srep10443. View

Hamel R, Dejarnac O, Wichit S, Ekchariyawat P, Neyret A, Luplertlop N . Biology of Zika Virus Infection in Human Skin Cells. J Virol. 2015; 89(17):8880-96. PMC: 4524089. DOI: 10.1128/JVI.00354-15. View

Retallack H, Di Lullo E, Arias C, Knopp K, Laurie M, Sandoval-Espinosa C . Zika virus cell tropism in the developing human brain and inhibition by azithromycin. Proc Natl Acad Sci U S A. 2016; 113(50):14408-14413. PMC: 5167169. DOI: 10.1073/pnas.1618029113. View

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

10.

Ferlenghi I, Clarke M, Ruttan T, Allison S, Schalich J, Heinz F . Molecular organization of a recombinant subviral particle from tick-borne encephalitis virus. Mol Cell. 2001; 7(3):593-602. DOI: 10.1016/s1097-2765(01)00206-4. View

11.

Foy B, Kobylinski K, Chilson Foy J, Blitvich B, da Rosa A, Haddow A . Probable non-vector-borne transmission of Zika virus, Colorado, USA. Emerg Infect Dis. 2011; 17(5):880-2. PMC: 3321795. DOI: 10.3201/eid1705.101939. View

12.

Ming G, Tang H, Song H . Advances in Zika Virus Research: Stem Cell Models, Challenges, and Opportunities. Cell Stem Cell. 2016; 19(6):690-702. PMC: 5218815. DOI: 10.1016/j.stem.2016.11.014. View

13.

Dowd K, Ko S, Morabito K, Yang E, Pelc R, DeMaso C . Rapid development of a DNA vaccine for Zika virus. Science. 2016; 354(6309):237-240. PMC: 5304212. DOI: 10.1126/science.aai9137. View

14.

Hioe C, Wrin T, Seaman M, Yu X, Wood B, Self S . Anti-V3 monoclonal antibodies display broad neutralizing activities against multiple HIV-1 subtypes. PLoS One. 2010; 5(4):e10254. PMC: 2858080. DOI: 10.1371/journal.pone.0010254. View

15.

Lavender K, Pang W, Messer R, Duley A, Race B, Phillips K . BLT-humanized C57BL/6 Rag2-/-γc-/-CD47-/- mice are resistant to GVHD and develop B- and T-cell immunity to HIV infection. Blood. 2013; 122(25):4013-20. PMC: 3862274. DOI: 10.1182/blood-2013-06-506949. View

16.

Zanluca C, de Melo V, Mosimann A, Santos G, Duarte Dos Santos C, Luz K . First report of autochthonous transmission of Zika virus in Brazil. Mem Inst Oswaldo Cruz. 2015; 110(4):569-72. PMC: 4501423. DOI: 10.1590/0074-02760150192. View

17.

Govero J, Esakky P, Scheaffer S, Fernandez E, Drury A, Platt D . Zika virus infection damages the testes in mice. Nature. 2016; 540(7633):438-442. PMC: 5432198. DOI: 10.1038/nature20556. View

18.

Sapparapu G, Fernandez E, Kose N, Cao B, Fox J, Bombardi R . Neutralizing human antibodies prevent Zika virus replication and fetal disease in mice. Nature. 2016; 540(7633):443-447. PMC: 5583716. DOI: 10.1038/nature20564. View

19.

Chang G, Davis B, HUNT A, Holmes D, Kuno G . Flavivirus DNA vaccines: current status and potential. Ann N Y Acad Sci. 2002; 951:272-85. View

20.

Danner R, Chaudhari S, Rosenberger J, Surls J, Richie T, Brumeanu T . Expression of HLA class II molecules in humanized NOD.Rag1KO.IL2RgcKO mice is critical for development and function of human T and B cells. PLoS One. 2011; 6(5):e19826. PMC: 3096643. DOI: 10.1371/journal.pone.0019826. View