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Humanized DRAG Mouse Model Holds Promise For Pre-Clinical Testing of Candidate HIV Vaccines

June 3, 2015
Researchers believe new findings will provide a new pre-clinical model to understand the early events in mucosal HIV infection and help to evaluate candidate HIV vaccines.

A new study led by MHRP researchers in collaboration with the Military Malaria Vaccine Program shows that T follicular helper cells (Tfh) accumulate in the gut and female reproductive tract of humanized DRAG mice, which are highly permissive to HIV infection. Researchers believe this will provide a new pre-clinical model to understand the early events in mucosal HIV infection and help to evaluate candidate HIV vaccines. Results were published today in Scientific Reports, a research publication from the publishers of Nature.

The Military Malaria Vaccine Program at the Naval Medical Research Center, which is co-located with the Walter Reed Army Institute of Research, developed the humanized DRAG (HLA-DR4.RagKO.IL2RγcKO.NOD) mouse for their research. While humanized mice have been used in medical research for many years, they have played a small role in HIV vaccine research due to limitations in their ability to generate functional T-cell responses in mucosal tissues during the course of HIV infection.  In this study, MHRP researchers demonstrate that humanized DRAG mice have a high level of reconstitution of human B and T cells in the gut and the reproductive tract. 

This humanized mouse model allowed researchers to study mucosal CD4+ T cells before and after HIV infection, with special emphasis on Tfh cells. Researchers believe a better understanding of Tfh cells and their interaction with B cells could be essential to the design of an effective vaccine.