Webinar: Humanized Mice in HIV Drug Discovery


     
hiv virus cells Human immunodeficiency virus (HIV) and acquired immune deficient syndrome (AIDS) caused by HIV continue to impact approximately 36.7 million people worldwide. In the United States alone it is estimated that 50,000 new HIV infections occur each year, and that nearly one in eight HIV carriers are unaware of their status.

Thanks to improvements in combined antiretroviral therapy (cART), HIV is no longer a death sentence. But despite decades of investigation, there is no cure for HIV or AIDS. Can humanized mice speed up HIV drug discovery, further improving quality of life for those living with HIV?

While several HIV animal models exist, the virus replicates poorly in most animal models including non-human primates. HIV is a human-specific virus, targeting human immune cells. Modification of the virus is often needed for effective infection in animal models which do not have human lymphocytes.

Unlike other models, human immune cells including T cells are present in humanized NOG mice. As reported by TransCure, stable and elevated HIV viral load in the blood can be observed without virus modification in human immune system engrafted NOG mice such as the huNOG.

To support HIV research, Taconic hosted an HIV Drug Discovery webinar with Dr. Patrick Nef (CEO) and Dr. Sebastien Tabruyn (CSO) of TransCure BioServices.

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TransCure is a contract research organization (CRO) providing support to the pharmaceutical and biotechnology companies through preclinical candidate selection, immunosafety, and efficacy in humanized mouse models related to inflammation, oncology, and infectious diseases.

As no GvH is observed and hCD45 chimerism is stable in humanized NOG, huNOG can be used for HIV latency and resistance study beyond 120 days.
In this exclusive Taconic webinar, Drs. Nef and Tabruyn discuss in detail how a humanized NOG mouse could be an in vivo model for HIV drug discovery, characterize anti-HIV prevention strategies, and investigate novel HIV eradication strategies.

TransCure's Guideline for Use of huNOG in HIV Research

Study Design:

  • Protective/vaccine prime, anti-HIV efficacy/combotherapy, rebound/latency, and resistance can be studies in humanized NOG

HIV strain:

  • Both cytopathic and cytolytic strain can be studied
    • TransCure discussed two HIV-1 strains in the presentation: R5/yu2 and X4/NL4-3 strains
  • Tropism: CCR5, CSCR4, or combined

Viral load:

  • ~106 copies/ml has been observed

Route of infection

  • IV, IP, and vaginal infections are possible

Route of Treatment

  • IV, IP, gavage, food pellet/drinking water has been tested

Endpoints/disease progression:

  • HIV viral load in blood by qPCR
  • Leukocyte population by flow cyometery
  • Survival rate and weight loss

Study Length

  • Long term resistance study is possible: ~120 days data were shown in the presentation

HARRT (highly active antiretroviral therapy)

  • Combination of raltegravir, lamivudine, tenofovir (food pellet at libidum) were used in the data shown
References and publications suggested by Drs. Nef and Tabruyn:
Ibeh at al. (2016) Humanized mouse as an appropriate model for accelerated global HIV research and vaccine development: current trend. Immunopharmacol Immunotoxicol. 7:1-13.
Araínga M, Su H, Poluektova LY, Gorantla S, Gendelman HE. (2016) HIV-1 cellular and tissue replication patterns in infected humanized mice. Sci Rep. 6:23513.
Veselinovic M, Neff CP, Mulder LR, Akkina R. (2012) Topical gel formulation of broadly neutralizing anti-HIV-1 monoclonal antibody VRC01 confers protection against HIV-1 vaginal challenge in a humanized mouse model. Virology. 25;432(2):505-10.
Nischang M, Sutmuller R, Gers-Huber G, Audigé A, Li D, Rochat MA, Baenziger S, Hofer U, Schlaepfer E, Regenass S, Amssoms K, Stoops B, Van Cauwenberge A, Boden D, Kraus G, Speck RF. (2012) Humanized mice recapitulate key features of HIV-1 infection: a novel concept using long-acting anti-retroviral drugs for treating HIV-1 PLoS One. 7(6).