Researchers have found what they think could be the key to a whole new way of treating and protecting against influenza—with monoclonal antibodies. If the discovery pans out, the approach could be used as a treatment for bird flu and seasonal flu and also as the basis for a vaccine against many different flu strains, including the H5N1 strain that has caused so much worry about a pandemic. To get the story, US News talked with Wayne Marasco, an associate professor of medicine in the department of cancer immunology and AIDS at the Dana Farber Cancer Institute, one of the developers of the new approach. Here's an edited version of the conversation:
You've identified human monoclonal antibod ies that lead the immune system's attack on a flu virus by attaching to specific points on it. How did th is discovery come about?
We were funded by the National Institutes of Health specifically to develop a therapy against bird flu. The surprising part of the story is that along the way we discovered that the antibodies we developed not only worked very efficiently against the bird flu but also worked very effectively against the seasonal flu strains that are circulating today.
Antibodies are a key part of the human immune system; they bind to viruses and other invaders and either immobilize them or tag them so other parts of the immune system can destroy them. But isn't one of the biggest problems in fighting flu that the viruses keep changing?
The influenza virus has developed a very clever decoy. Its coat protein [on the outside of the flu virus] looks like a lollipop. Your immune system is really directed against the big globular head of the lollipop because it's there in large supply, but that's the part that the virus can change easily. This is the reason why we end up having to get seasonal vaccinations. All of the vaccines are directed against the globular head, and the globular head can change.
Our vaccine is directed against the lollipop stick, which actually contains the machinery that allows the virus to enter cells. This is what allowed us to make this significant scientific advance—to identify a new Achilles' heel in the virus's coat protein.
How do you know that this antibody works against both bird flu and seasonal flu?
We tested the antibody against bird flu, against 1918 pandemic flu; we tested it against all 10 different types of flu viruses, multiple strains, both in tissue culture and in animals. The antibody was not only active in preventing infection; you could give it to animals that got a lethal dose of the flu virus as late as three days after infection, when they were clearly getting sick, and they recovered and survived.
This is exciting science, but it's not yet a cure for the flu. What's the next step?
With the additional testing that's required, there should be a very potent anti-influenza drug that will come out of this work. We are planning to be in clinical trials in the 2011-2012 flu season, which is about as fast as you can go. This is the actual drug that will wind up going into people. The antibodies are produced in cell factories. We need to pass our antibodies on to a manufacturer that will complete the animal studies and conduct the clinical trials.
How would this treatment work, if it's approved as a flu treatment?
The antibodies have to be given by injection or inhalation, and they last in your body for 21 days. Monoclonal antibodies are currently being used to treat cancers and inflammatory diseases, including Herceptin for the treatment of breast cancer, Avastin or Erbitux for the treatment of colon cancer, and Retuxin for the treatment of lymphoma.
The other question is whether we can turn this into a universal vaccine. The research involved in making that next step will probably take three to five years. The goal will be to develop lifelong immunity to flu, rather than developing seasonal immunity as we do now.