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Biomedicine

Arming the Immune System against H1N1

Researchers are working to treat pandemic flu by recruiting a patient’s own immune cells.

Viruses multiply incredibly quickly once they’ve infected their victim–so fast that antiviral medications such as Tamiflu are only effective if given during the first few days of an infection. After that, the viral load is just too high for a single drug to fight off. But researchers are working on a treatment for the H1N1 virus (or swine flu) that uses a different approach. Rather than disabling the virus with a drug, they’re creating a vaccine that can activate and steer a patient’s own immune cells to attack the invader.

Defense mechanism: Researchers creating a new vaccine against H1N1 hope to harness the power of the immune system’s dendritic cells (one such cell is shown above in blue), which are responsible for directing the body’s immune response.

Scientists at the Vienna, VA-based Cel-Sci have created a screening platform, called LEAPS (Ligand Epitope Antigen Presentation System) that identifies epitopes–small pieces of a virus that can be used to elicit very specific immune reactions. The DNA segments that make up these epitopes are so short–just eight to 30 amino acids long–that they can be re-created in the lab. Then the Cel-Sci researchers take those segments and attach them to another small molecule–an immune-cell-binding ligand that guides the complex straight to the immune cells in charge of initiating and directing an immune reaction.

The ligand-bound epitope is guided directly to immature dendritic cells, so named for tiny tentacles that reach out in every direction from the main cell body. Dendritic cells are the immune system’s conductors, responsible for initiating and guiding the fight against invaders like the influenza virus. Immature dendritic cells are prompted to mature by the presence of these invaders; the mature dendritic cells then activate T cells, which in turn stimulate very specific immunity against the virus.

“It’s like a live virus vaccine–and more effective–but without the live virus,” says Kenneth Rosenthal, an immunologist at Northeastern Ohio Universities Colleges of Medicine and Pharmacy who has collaborated with the Cel-Sci team.

So far, the company has tested the LEAPS system in mice with herpes and arthritis, and found the approach to be successful in modulating the rodents’ immune responses.

“The LEAPS technology allows you to drive an immune response in a desired direction,” says Cel-Sci director and CEO Geert Kersten. “It’s about modulating an immune response. That’s important, because it’s also possible to rev up the immune system and have no effect whatsoever.”

Now the company is turning its attention to H1N1. In research that has been fast-tracked by the U.S. Food and Drug Administration, Cel-Sci has created a peptide that it believes will direct the human immune system to fight the virus directly. In collaboration with physicians at Johns Hopkins University’s School of Medicine, researchers are collecting blood from 20 patients hospitalized with H1N1, and 20 healthy controls, then stimulating the blood with their peptide to see if they can initiate the appropriate immune responses.

“We need to find the kinds of responses that have commonly been associated with an ultimate positive outcome,” Kersten says. “If we see those kinds of responses, then, based on FDA discussions, we expect to be able to do a randomized clinical trial.” The group hopes to be able to move forward as soon as their results come in.

Kersten is optimistic. “We have a way, at least in other diseases, of directing the cellular immune response without the production of pro-inflammatory cytokines,” he says, referring to signaling molecules that can incite unwanted inflammation. Cytokines are produced by the body’s own immune cells, but when their production goes unchecked and ramps up too high, they can cause the body to overreact to a virus. Cel-Sci’s approach circumvents such a response.

Cel-Sci creates its peptide using epitopes from the small segments of flu virus that don’t mutate, and which could therefore be used to treat H1N1 even as it changes over the course of the year–such an approach could also be effective against other strains of flu, such as avian (H5N1) and even 1918 pandemic influenza.

Using dendritic cells to direct immune response is an attractive mechanism, says Noel Rose, director of the Center for Autoimmune Disease Research at the Johns Hopkins Bloomberg School of Public Health. “This would have applications far beyond H1N1,” he says. “It would be a nice way of having a person make his own vaccine.”

Rose was not involved in the trial, but his lab will analyze the cytokine results. “I have no idea what to expect, because we don’t know what cytokines are going to be produced.” Even so, he says, “I think it could be really interesting.”

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