TY - JOUR
T1 - A single-dose live-attenuated vaccine prevents Zika virus pregnancy transmission and testis damage
AU - Shan, Chao
AU - Muruato, Antonio E.
AU - Jagger, Brett W.
AU - Richner, Justin
AU - Nunes, Bruno T.D.
AU - Medeiros, Daniele B.A.
AU - Xie, Xuping
AU - Nunes, Jannyce G.C.
AU - Morabito, Kaitlyn M.
AU - Kong, Wing Pui
AU - Pierson, Theodore C.
AU - Barrett, Alan D.
AU - Weaver, Scott C.
AU - Rossi, Shannan L.
AU - Vasconcelos, Pedro F.C.
AU - Graham, Barney S.
AU - Diamond, Michael S.
AU - Shi, Pei Yong
N1 - Funding Information:
We thank colleagues at University of Texas Medical Branch for helpful discussions and support during the course of this study. We also thank J.P. Todd and R. Bailer for help with the nonhuman primate studies and sample processing. P.-Y.S. lab was supported by University of Texas Medical Branch (UTMB) startup award, University of Texas STARs Award, CDC grant for the Western Gulf Center of Excellence for Vector-Borne Diseases, Pan American Health Organization grant SCON2016-01353, the Kleberg Foundation award, UTMB CTSA UL1TR-001439 and NIH grant AI127744. K.M.M., W.-P.K., B.S.G., and T.C.P. are funded through intramural funding from the National Institute of Allergy and Infectious Diseases. This research was also partially supported by NIH grant AI120942 to S.C.W. and grants AI073755, AI104972, and AI106695 from the NIH to M.S.D. P.F.C.V. was suported by projects of CAPES (Zika Fast-Track) and CNPq: grants 440405/2016-5, and 303999/2016-0 from the Ministry of Science and Technology of Brazil and by the Ministry of Health.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85029754852&partnerID=8YFLogxK
U2 - 10.1038/s41467-017-00737-8
DO - 10.1038/s41467-017-00737-8
M3 - Article
C2 - 28939807
AN - SCOPUS:85029754852
VL - 8
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 676
ER -