Chikungunya AG129 Mouse Model

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus endemic in Africa and Asia that causes a debilitating disease in over 2 million people every year in explosive outbreaks. Currently there are no vaccines or therapeutics available for this emerging virus. IBT Bioservices has established a lethal model for this disease based on previous publication (Partidos, 2011).

This model utilizes AG129 mice deficient in IFN α/β and IFN γ signaling and an attenuated strain of CHIKV (181/25). It is an ideal model for testing drug and vaccine candidates and has the following advantages:

  • Lethal challenge dose established allowing efficacy testing using morbidity and mortality endpoints.
  • Virus causes necrotic histopathological changes in the spleens of infected mice.
  • Utilizes an attenuated strain (CHIKV 181/25) that is safe to handle in BSL-2 environment thereby avoiding high costs of BSL-3 studies.
  • Successfully used to demonstrate efficacy of CHIKV experimental vaccine candidates.
  • Adoptive transfer of hyperimmune serum protects against lethal challenge suggesting the utility of the model to evaluate therapeutic candidates.

Chikungunya

Fig. 1 Survival after challenge with INFV H1N1 A/Pert/261/2009 (Tamiflu-resistant strain). Inoculum 1xLD90=1.0E+05 PFU/mouse
Survival after challenge with INFV H1N1 A/Pert/261/2009 (Tamiflu-resistant strain) 1.0E+05 PFU/mouse
Survival and weight change in BALB/c mice challenged with INFV A/ Texas/36/91 (H1N1) and treated with antiviral Osletamivir Phosphate (Tamiflu)
Lung viral load and Survival (30 % weight loss cut-off) in BALB/c mice challenged with INFV H3N2 A/HK/1/68.

Alpha (UK) – B. 1.1.7 / 501Y.V1

amino acid mutations: del69–70 HV, del144 Y, N501Y, A570D, D614G, P681H, T761I, S982A, D1118H

Beta (South Africa) – B.1.351

amino acid mutations: K417N, E484K, N501Y, D614G, A701V

Gamma (Brazil) – P.1

amino acid mutations: L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I

Epsilon (Ca, USA) B.1.427

amino acid mutations: L452R, D614G

SARS-CoV-2 Parental Strain Wild Type (Wuhan)
SARS-CoV-2 D614G Variant

amino acid mutations: D614G

Epsilon (Ca, USA) B.1.429

amino acid mutations: S13I, W152C, L452R, D614G

SARS-CoV-2 Delta Variant

amino acid mutations: L452R, E484Q