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Zika Virus Animal Models for Preclinical Efficacy Testing

Zika Virus (ZIKV) is a mosquito-borne flavivirus associated with the recent outbreak of febrile disease across the Americas.

Zika infection causes Zika fever and infection during pregnancy is hypothesized to cause microcephaly in neonates. The IFN / and IFN receptor deficient AG129 mouse model using ZIKV FSS13025 strain is based on previously described model (Rossi, et al., 2016). AG129 mice aged 6-8 week challenged with FSS13025 strain have a mean time to death of 11-12 days post infection. This model provides a biologically relevant approach for studying ZIKV infection without relying on intracerebral inoculation. It has several advantages, including the ability to induce lethal and non-lethal infections without requiring mouse-adapted ZIKV strains.
Additionally, consistent symptoms are associated with disease development, making it a well-suited model for screening anti-viral compounds and evaluating vaccine candidates. IBT provides models using the FSS13025 and PRVABC59 Asian Pacific lineage strains.

KEY FEATURES

Animal Background: Challenge Route: Mean Time to Death: Standard Readouts:

AG129

Subcutaneous (SC)

Strain dependent

Weights, health and survival
Other Readouts

CPE Assay, HAI Assay, PRNT, Microneutralization assay,
Pseudovirus neutralization assay, ELISA, Luminex, Flow cytometry, viremia assessment of various organs including the reproductive system
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Description: Disease progression of ZIKA FSS13025 administered via the subcutaneous (SC) route in AG129 mice (n=15). All mice succumbed to infection by day 12 of the study when challenged with 1.00E+04 PFU/mouse.

Description: Reproductive tissues collected from infected mice 4-, 6-, and 8- days post infection were analyzed for viral load via plaque assay. Viral load in ovaries peaked at 6 days post infection while the viral load in testes continued to rise even at 8 days post infection.

Description: Serum and tissues collected from infected mice 2-, 4-, 6-, and 8-days post infection were analyzed for viral load via plaque assay. Serum viral load peaked at 4 days post infection while most tissue viral load peaked at 6 days post infection. IN LN= Inguinal lymph nodes. AUX LN= Auxiliary lymph nodes.

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