Protective Efficacy of Nucleic Acid Vaccines Against Transmission of Zika Virus During Pregnancy in Mice.
J Infect Dis
; 220(10): 1577-1588, 2019 10 08.
Article
in En
| MEDLINE
| ID: mdl-31260518
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Viral Vaccines
/
Infectious Disease Transmission, Vertical
/
Vaccines, DNA
/
Zika Virus
/
Zika Virus Infection
Limits:
Animals
/
Pregnancy
Language:
En
Journal:
J Infect Dis
Year:
2019
Document type:
Article