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

HIV Mouse Infection as in Human

HIV Mouse Infection as in Human

Typical data illustrating :

  • Efficacy of HAART
  • Rebound after treatment cessation

Selection For Best Clinical Candidates

  • huNOG infected with Yu2 HIV Strain
  • Anti-Viral treatment initiated 5 weeks after infection

Cytolytic and Cytostatic HIV Strains

  • huNOG infected with cytolytic NL4-3 and cytostatic Yu2 HIV Strain
  • Percentage of CD4+ cells among CD3+ cells determined by Flow Cytometry analysis

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

Find out our fee-for-services about: Cancer/Immuno-oncology/PDX, Inflammation/IBD.


Share this!