In the so-far unsuccessful effort to develop an HIV vaccine, scientists have tried numerous avenues to stop the AIDS-causing virus. They’ve tried exposing patients to a vaccine from the killed virus, to proteins from parts of the virus, to triggering disease-fighting T cells to go after the infection, and more.

On Monday, scientists from The Scripps Research Institute in La Jolla announced they had conceptually demonstrated an entirely new method of blocking HIV. Moreover, they have teamed up with City of Hope hospital in the Los Angeles area — a prominent center of HIV therapy development — to develop the method so it can be tested in HIV patients.

The proof of concept was performed using an antibody that can block a cellular portal called a receptor. The receptor is used by a rhinovirus, one of many that cause the common cold, to infect cells. The researchers are porting this over to HIV, and some of that work was also discussed in the study.

If the vaccine-like technology works — and it will be years before it will be ready for patients — it would cure them of HIV disease, said Scripps Research professor Richard Lerner, who led a study of the technology. Their immune systems would no longer be ravaged by HIV.


The study, published in the Proceedings of the National Academy of Science, can be found at j.mp/antibodycd4. Lerner was senior author. Jia Xie, also of Scripps Research, was the first author.

Two HIV researchers not involved in the study, Marcella Flores of the American Foundation for AIDS Research and Paula Cannon of the University of Southern California, said it represents a remarkable feat of basic science research.

However, Flores and Cannon cautioned that years more work needs to be done before it can be tested in people.

The “vaccine,” Lerner said, is an HIV-blocking antibody genetically engineered into blood-forming stem cells, which give rise to immune cells. In the lab, the method blocks the virus from using an important molecular portal called the CD4 receptor to infect the T cells.


ln the rhinovirus work, the antibody was further demonstrated to selectively inhibit viral infection, while not disabling normal cellular receptor functions. If this selectivity can be achieved for blocking HIV from attaching to CD4 in clinical trials, it would allow the receptor to perform vital immune functions.

Engineering that selectivity with HIV and CD4 will be quite difficult, Cannon said, so the researchers have a lot of work ahead of them.

Cannon is working on another approach to engineering HIV resistance in partnership with City of Hope and Sangamo Biosciences. That method is already in clinical trials, aided by funding from CIRM, California’s stem cell agency.

Antibodies normally function by swarming through the blood in search of pathogens to attack. Lerner, a world-recognized expert in antibodies, said anchoring the antibody where it’s needed is much more effective in ensuring that HIV will be blocked.


Many more viruses could be blocked with the technology, Lerner said, so this approach represents a new antiviral platform that could generate many therapies.

Cells to be treated with the technology would be removed from patients, genetically edited, then reinfused into the patients. The resistant cells would replace those killed or damaged by HIV, producing an HIV-resistant immune system.

City of Hope is committed to helping the Scripps scientists do the work to translate the research into a usable therapy, said John Zaia of the medical center.

However, it’s likely that the Scripps technology will be used to block another receptor HIV uses, called CCR5, said Zaia, director of the Center for Gene Therapy in the Hematological Malignancy and Stem Cell Transplantation Institute at City of Hope.


The CCR5 receptor isn’t essential, in fact people born without it have normal health, Zaia said. So completely blocking that receptor shouldn’t case any serious side effects.

City of Hope is already clinically testing disabling CCR5, using the Sangamo approach to HIV therapy. That approaches uses an older and more tested gene editing technology called zinc finger nucleases.

With the center’s expertise in this field, The Scripps Research Institute’s science is a natural fit, Zaia said.


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