A single-dose live-attenuated vaccine prevents Zika virus pregnancy transmission and testis damage

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

doi:10.1038/s41467-017-00737-8

A single-dose live-attenuated vaccine prevents Zika virus pregnancy transmission and testis damage

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

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86 Scopus citations

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.

Original language	English (US)
Article number	676
Journal	Nature communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-00737-8
State	Published - Dec 1 2017

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Shan, C., Muruato, A. E., Jagger, B. W., Richner, J., Nunes, B. T. D., Medeiros, D. B. A., Xie, X., Nunes, J. G. C., Morabito, K. M., Kong, W. P., Pierson, T. C., Barrett, A. D., Weaver, S. C., Rossi, S. L., Vasconcelos, P. F. C., Graham, B. S., Diamond, M. S., & Shi, P. Y. (2017). A single-dose live-attenuated vaccine prevents Zika virus pregnancy transmission and testis damage. Nature communications, 8(1), Article 676. https://doi.org/10.1038/s41467-017-00737-8

Shan, C, Muruato, AE, Jagger, BW, Richner, J, Nunes, BTD, Medeiros, DBA, Xie, X, Nunes, JGC, Morabito, KM, Kong, WP, Pierson, TC, Barrett, AD , Weaver, SC , Rossi, SL, Vasconcelos, PFC, Graham, BS, Diamond, MS & Shi, PY 2017, 'A single-dose live-attenuated vaccine prevents Zika virus pregnancy transmission and testis damage', Nature communications, vol. 8, no. 1, 676. https://doi.org/10.1038/s41467-017-00737-8

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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.",

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A single-dose live-attenuated vaccine prevents Zika virus pregnancy transmission and testis damage

Abstract

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