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- Title
Protective Efficacy of Nucleic Acid Vaccines Against Transmission of Zika Virus During Pregnancy in Mice.
- Authors
Jagger, Brett W; Dowd, Kimberly A; Chen, Rita E; Desai, Pritesh; Foreman, Bryant; Burgomaster, Katherine E; Himansu, Sunny; Kong, Wing-Pui; Graham, Barney S; Pierson, Theodore C; Diamond, Michael S
- Abstract
Zika virus (ZIKV) caused an epidemic of congenital malformations in 2015-2016. Although many vaccine candidates have been generated, few have demonstrated efficacy against congenital ZIKV infection. Here, we evaluated lipid-encapsulated messenger RNA (mRNA) vaccines and a DNA plasmid vaccine encoding the prM-E genes of ZIKV in mouse models of congenital infection. Although the DNA vaccine provided comparable efficacy against vertical transmission of ZIKV, the mRNA vaccines, including one that minimizes antibody-dependent enhancement of infection, elicited higher levels of antigen-specific long-lived plasma cells and memory B cells. Despite the induction of robust neutralizing antibody titers by all vaccines, breakthrough seeding of the placenta and fetal head was observed in a small subset of type I interferon signaling-deficient immunocompromised dams. In comparison, evaluation of one of the mRNA vaccines in a human STAT2-knockin transgenic immunocompetent mouse showed complete protection against congenital ZIKV transmission. These data will inform ongoing human ZIKV vaccine development efforts and enhance our understanding of the correlates of vaccine-induced protection.
- Publication
Journal of Infectious Diseases, 2019, Vol 220, Issue 1, pN.PAG
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiz338