Zika virus (ZIKV) is an emerging mosquito-borne virus that is causing explosive outbreaks. While asymptomatic in most healthy adults, ZIKV infection of pregnant women causes severe developmental complications of fetuses, including fetal death, microcephaly and a variety of other neurological complications. No animal model of fetal ZIKV infection is currently available. Because adult rhesus macaques can be infected with Zika virus, including isolates from recent outbreaks, it is important to investigate if ZIKV infection of fetal macaques has similar detrimental effects. The development of a nonhuman primate model of fetal pathogenesis, that affords precise experimental control, is critical to (i) determine the mechanisms of how ZIKV infection affects the developing fetus, including the fetal brain and other parts of the central nervous system, and (ii) to develop and screen intervention strategies, including vaccines and therapeutics. The proposed pilot studies, aimed at demonstrating proof-of-concept, have been designed to test whether ZIKV infection initiated at different times of gestation can recapitulate the spectrum of outcomes described in ZIKV-infected pregnant women, and determine how the timing of ZIKV infection in pregnancy associates with markers of viral replication, viral distribution, immune markers and pathology. The overarching objective of the proposed work is to develop a NHP model of fetal pathogenesis, ultimately allowing scientists to expedite clinical trials with the ultimate goal of curtailing the ZIKV pandemic as quickly as possible.

Public Health Relevance

The project is aimed at developing a nonhuman primate model of maternal and fetal Zika virus infection. Such a model is critical to develop better tools to monitor infection and to develop safe and effective treatments and vaccines.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI129479-02
Application #
9386071
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Challberg, Mark D
Project Start
2016-11-14
Project End
2019-10-31
Budget Start
2017-11-01
Budget End
2019-10-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of California Davis
Department
Veterinary Sciences
Type
Primate Centers
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Dudley, Dawn M; Van Rompay, Koen K; Coffey, Lark L et al. (2018) Miscarriage and stillbirth following maternal Zika virus infection in nonhuman primates. Nat Med 24:1104-1107
Coffey, Lark L; Keesler, Rebekah I; Pesavento, Patricia A et al. (2018) Intraamniotic Zika virus inoculation of pregnant rhesus macaques produces fetal neurologic disease. Nat Commun 9:2414
Keeffe, Jennifer R; Van Rompay, Koen K A; Olsen, Priscilla C et al. (2018) A Combination of Two Human Monoclonal Antibodies Prevents Zika Virus Escape Mutations in Non-human Primates. Cell Rep 25:1385-1394.e7