Jeff Lifson, M.D., director of the AIDS and Cancer Virus Program
By Frank Blanchard, Staff Writer, and Jeff Lifson, Guest Writer
Researchers are working to develop a more authentic animal model of human immunodeficiency virus (HIV) infection and AIDS that is expected to speed up studies of experimental treatments and vaccines.
Under a recently signed contractor Cooperative Research and Development Agreement (cCRADA) between Leidos Biomedical Research (under the former name of SAIC-Frederick) and the Aaron Diamond AIDS Research Center (ADARC) in New York City, the two groups will extend their longstanding collaboration to further develop and refine an improved animal model for AIDS.
To date, different species of macaque monkeys have provided the best animal models for AIDS-relevant studies. However, the HIV-1 virus that infects humans does not productively infect or cause disease in monkeys, so researchers have had to use related monkey viruses, known as simian immunodeficiency viruses (SIVs).
SIV infection of macaques demonstrates key features of human HIV-1 infection. Such models have been useful for studies of disease mechanisms and for evaluating experimental approaches for treatment and prevention of infection using vaccines and other methods.
Although SIVs are related to HIV, they are imperfect models.
Engineering a Virus that Mimics HIV in Nonhuman Primates
Many vaccine studies use macaques challenged with SIV, especially for proof-of-concept studies to test whether a new vaccine approach is effective. But even when such a study produces positive results, researchers typically have to test whether the corresponding HIV versions of the vaccines induce comparable immune responses in macaques before proceeding to initial clinical studies.
In addition, while many anti-HIV drugs work against SIV, some don’t work as well, and some don’t work at all against the simian viruses. Clearly, a nonhuman primate model utilizing something closer to HIV itself would be a major advance.
The collaboration enables the scientists to use emerging information about host defense factors (which limit the ability of HIV to replicate in monkey cells) to engineer minimally modified viruses, called simian tropic HIVs (stHIVs). The engineered viruses are almost completely HIV but contain small modifications designed to help the virus overcome the host defense factors in macaque cells.
Through such design and engineering approaches, combined with adaptation in infected macaques, the scientists are developing a new model based on viruses that are almost completely HIV and are able to infect macaques and cause AIDS. By reproducing key features of human HIV infection, such a model will represent a major advance for the field, enabling faster and better studies of vaccines and experimental treatments.
Principal investigators are Theodora Hatziioannou, Ph.D., of ADARC, and Jeff Lifson, M.D., of the Frederick National Laboratory’s AIDS and Cancer Virus Program. Hatziioannou’s group will generate and characterize variants of stHIV, while Lifson’s lab will conduct the animal testing (analyses of blood, cells, and tissues) and viral sequence analyses.
cCRADA Mechanism Streamlines Collaborations
The cCRADA enables Leidos Biomedical Research to collaborate directly with external organizations and receive funds to offset associated costs. The cCRADA also enables Frederick National Laboratory to streamline collaborations and to manage intellectual property for technology transfer. As a result, extramural and commercial researchers will have greater access to the national lab’s science, technology, and expertise.
Jeff Lifson, M.D., is the director of the AIDS and Cancer Virus Program.