anti-HIV hu-mouse models

HIV is a human specific virus targeting human CD4+ circulating lymphocytes. During the past 10 years, the development of the reconstitution of a full functional human immune system in immune deficient mouse models has provided the opportunity to setup HIV hu-mouse models. Compared to SIV monkey models, HIV mice are cheaper, safer, and ethically acceptable. Current tri-therapy are showing similar efficacy on HIV mice than on HIV patients and combotherapy designs can be executed nicely with HIV hu-mice.

HIV hu-mice

Hu-mice (NOG, NCG, BRG, NSG) can be infected with various strain of HIV and few weeks later, in vivo profiling of new anti-HIV drug candidates can be initiated. Typically, we assess efficacy, resistance, rebound, latency and combotherapy strategies, as HIV infection leads to a stable and elevated viral load in the blood. Conventional HAART therapy for 3 weeks decreases by 95% the circulating HIV viral load, and treatment cessation induces a rebound as observed in HIV/AIDS patients. Different HIV strains can be used for the successful infection of hu-mice. Cytolytic and cytopathic effects have been studied on human CD4 positive lymphocytes from HIV mice.

HIV infection

Strengh of HIV Mouse Models

We are convinced that using HIV hu-mouse models is the most efficiency process for getting preclinical candidate efficacy translational data for further clinical testing:

• Full blown HIV infection (106-107 HIV load/ml) within 4-5 weeks
• 95% decrease of HIV load upon HAART treatment in <14 days
• IP, IV or vaginal routes of infection
• R5 and X4 tropism reconstitution
• Cytolytic activity of X4-HIV strain as in human
• Combotherapy strategy for selection of best clinical candidates/schedule/regimen
• Latency and rebound protocols for disease management with mAbs & small NCE’s

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