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Abstract
A NEW MURINE MODEL FOR TESTING HIV-1 PROTECTIVE VACCINES
M. Ayash-Rashkovsky1, G. Borkow1, H. Davis2, R.B. Moss3, Z. Bentwich1
1Hebrew University Hadassah Medical School, Jerusalem, Israel, 2Coley Pharmaceutical Group, Ottawa, Canada, 3Immune Response Corporation, San Diego, USA
Purpose: To establish and characterize a new murine model for HIV-1 infection and rapid testing of candidate vaccines.
Methods: Trimera mice (irradiated normal animals rescued by murine SCID bone marrow and transplanted with human PBMC), were infected with different clades of cell-free T- and M- tropic HIV-1. HIV specific antibody respopnse was determined by ELISA, and cellular response by intracellular staining, following HIV-1 infection and immunizations with autologous human dendritic cells (DCs) pulsed with gp120-depleted HIV-1 immunogen, with or without CpG ODN. Immunized mice were studied for their ability to resist infection with HIV-1.
Results Viremia, viral replication, and proviral HIV-1 DNA were established in all groups of Trimera mice. Rapid loss of human CD4+ T-cells, decrease in CD4/CD8 ratio, and increased T-cell activation, accompanied HIV-1 infection. Elevation of HIV specific human IgG and IgM occurred in all HIV-1 infected mice and in mice immunized with HIV-1 immunogen with or without CpG ODN. Proportion of IFN-( positive human cells obtained from mice immunized with either immunogen alone, or immunogen with CpG ODN, increased 2-3, and 5-8 times, respectively, following exposure to the immunogen. Immunized mice were successfully protected from infection following challenge with HIV-1.
Conclusions: 1) The new murine (Trimera) model for HIV infection is distinct from all previous murine models of HIV infection in its ability to generate specific immunity to HIV. 2) Protective immunity to HIV was generated in the animals and makes this model an attractive tool for fast testing of candidate HIV vaccines.
The 2nd IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
515
Suggested Citation
" M. Ayash-Rashkovsky , et al.
A NEW MURINE MODEL FOR TESTING HIV-1 PROTECTIVE VACCINES.
Poster:
The 2nd IAS Conference on HIV Pathogenesis and Treatment:
Abstract no.
515"
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