Southern Research ZIKV AG129 mouse model

AG129 Mouse Model:

AG129 mice were selected because they are highly susceptible to infection when challenged with the Puerto Rican strain of ZIKV, PRVABC59. As such, they serve as an ideal candidate for observing how the virus infection progresses in a living model. More specifically, the model is 100% lethal at subcutaneous challenge dose 1×101-1×105 PFU, and AG129 exhibit pronounced clinical signs of infection, such as weight loss and neurological indications that were not otherwise exhibited in other species.

In this sense, the NHP reacted to Zika in a manner much more similar to humans.

While cynomolgus macaque models are essential for studying the safety and efficacy of candidate ZIKV vaccines,  clinical disease model such as AG129 provide a very useful tool for efficacy evaluation of ZIKV antivirals in “trigger to treat” testing.

Key findings, to date:

  • AG129 model is 100% lethal after subcutaneous challenge dose 1×101-1×105 PFU of the PRBABC59 strain.
  • Neurological signs are detected in a majority of the animals tested.
  • Presence of high serum viral load and high neutralizing antibodies (PRNT50) were evident in all AG129 mice tested.
  • The model is suitable for prophylactic and therapeutic antiviral drug efficacy evaluation.
  • In addition to NHP model, AG129 offers an alternative model for testing candidate Zika vaccines.

Preliminary Data (updated 8/3/2016):

AG129 mouse model_5wk Survival following Subcutaneous Challenge with PRVABC59

5-weeks-old male and female AG129 mice were subcutaneously challenged with 1×101-1×105 PFU of Zika virus PRVABC59 strain (N=5 per group). 100% lethality was detected in all groups and neurological signs were detected in a majority of the animals.

 

AG129 mouse model_Changes in bodyweight following ZIKV Infection

Percentage change in AG129 bodyweight following ZIKV Infection (PRVABC59) Groups 1-5.

 

AG129 mouse model_Viral Load by qRT-PCR

AG129 terminal serum viral load by qRT-PCR following challenge with ZIKV PRVABC59

 

In an effort to identify a vaccine for the Zika virus (ZIKV), Southern Research is running multiple animal model studies independently and through a contract with the NIAID in non-human primates (NHP).