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 () and Pei-Yong Shi ()
Additional contact information
Chao Shan: University of Texas Medical Branch
Antonio E. Muruato: University of Texas Medical Branch
Brett W. Jagger: Washington University School of Medicine
Justin Richner: Washington University School of Medicine
Bruno T. D. Nunes: University of Texas Medical Branch
Daniele B. A. Medeiros: University of Texas Medical Branch
Xuping Xie: University of Texas Medical Branch
Jannyce G. C. Nunes: University of Texas Medical Branch
Kaitlyn M. Morabito: National Institutes of Health
Wing-Pui Kong: National Institutes of Health
Theodore C. Pierson: National Institutes of Health
Alan D. Barrett: University of Texas Medical Branch
Scott C. Weaver: University of Texas Medical Branch
Shannan L. Rossi: University of Texas Medical Branch
Pedro F. C. Vasconcelos: Ministry of Health
Barney S. Graham: National Institutes of Health
Michael S. Diamond: Washington University School of Medicine
Pei-Yong Shi: University of Texas Medical Branch

Nature Communications, 2017, vol. 8, issue 1, 1-9

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00737-8

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