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 Barrett, Scott Weaver, Shannan Rossi, Pedro F.C. Vasconcelos, Barney S. Graham, Michael S. Diamond, Pei-Yong Shi

Research output: Contribution to journalArticle

48 Citations (Scopus)

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 languageEnglish (US)
Article number676
JournalNature Communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

Fingerprint

vaccines
testes
Attenuated Vaccines
pregnancy
viruses
Viruses
Testis
damage
Pregnancy
dosage
infectious diseases
mice
Vaccines
reproductive systems
Oligospermia
Fetal Death
primates
Immunization
Viral RNA
3' Untranslated Regions

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

A single-dose live-attenuated vaccine prevents Zika virus pregnancy transmission and testis damage. / Shan, Chao; Muruato, Antonio E.; Jagger, Brett W.; Richner, Justin; Nunes, Bruno T.D.; Medeiros, Daniele B.A.; Xie, Xuping; Nunes, Jannyce G.C.; Morabito, Kaitlyn M.; Kong, Wing Pui; Pierson, Theodore C.; Barrett, Alan; Weaver, Scott; Rossi, Shannan; Vasconcelos, Pedro F.C.; Graham, Barney S.; Diamond, Michael S.; Shi, Pei-Yong.

In: Nature Communications, Vol. 8, No. 1, 676, 01.12.2017.

Research output: Contribution to journalArticle

Shan, C, Muruato, AE, Jagger, BW, Richner, J, Nunes, BTD, Medeiros, DBA, Xie, X, Nunes, JGC, Morabito, KM, Kong, WP, Pierson, TC, Barrett, A, Weaver, S, Rossi, S, Vasconcelos, PFC, Graham, BS, Diamond, MS & Shi, P-Y 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
Shan, Chao ; Muruato, Antonio E. ; Jagger, Brett W. ; Richner, Justin ; Nunes, Bruno T.D. ; Medeiros, Daniele B.A. ; Xie, Xuping ; Nunes, Jannyce G.C. ; Morabito, Kaitlyn M. ; Kong, Wing Pui ; Pierson, Theodore C. ; Barrett, Alan ; Weaver, Scott ; Rossi, Shannan ; Vasconcelos, Pedro F.C. ; Graham, Barney S. ; Diamond, Michael S. ; Shi, Pei-Yong. / A single-dose live-attenuated vaccine prevents Zika virus pregnancy transmission and testis damage. In: Nature Communications. 2017 ; Vol. 8, No. 1.
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