Focus on the Flu : Preventing, Vaccine

by National Institute of Health

(Page 3 of 15)

Do-it-Yourself Flu Vaccine Might Protect in a Pandemic

For people who find an annual flu shot inconvenient or scary-and there may be quite a few, given that nearly two-thirds of Americans missed their flu vaccine last year-help may be on the way.

NIAID-funded researcher Richard Gillespie, B.S., president and co-founder of Pharma-Pen, Inc. of Athens, TX, is developing a vaccine delivery system that would no longer require a trip to the doctor. That, and it looks about as menacing as a ballpoint pen.

Mr. Gillespie's device, called the "auto-injector," would enable a person to self-administer a flu vaccine in seconds. The auto-injector houses a hypodermic needle that remains safely hidden away in its holder until a button is pushed. Once that happens, the needle instantly extends into the injection site, injects the vaccine, and retracts back into its case, ready to be thrown away.

"It happens so fast, I didn't feel a thing," says Mr. Gillespie, about his experience with the current prototype.

Not only could the auto-injector be useful to seniors, people with disabilities, and people in rural areas who may have trouble getting to the doctor, but it could be broadly distributed in the event of a pandemic, thereby eliminating the need for large numbers of people to transport themselves to centralized immunization stations.

In late 2004, Pharma-Pen received approval for a version of the device from the U.S. Food and Drug Administration.

A clinical trial will be conducted to determine if an injection into the fat layer just beneath the skin would immunize as well as an injection deeper into the muscle, which would require a longer needle and would carry more risk for injury. Researchers also are investigating if the self-administered vaccine produces the same results as the traditionally administered vaccine.

A Nasal Spray Flu Vaccine

FluMist is a licensed nasal spray flu vaccine that may offer several potential advantages over the flu shot. FluMist is based on live influenza viruses that have been weakened (attenuated) so they can't cause the flu. Because the FluMist vaccine contains live viruses, it may stimulate a broader immune response than the current vaccine, which contains proteins from inactivated, or "killed" viruses. The live vaccine viruses also have been selectively grown in the lab over many generations at increasingly cooler temperatures. This "cold adaption" is a double safety measure, preventing the viruses from spreading beyond the relatively cool upper respiratory tract. Finally, the FluMist vaccine is administered as a spray into the nose, which adults and especially children say is more pleasant than getting the current flu shot.

The National Institute of Allergy and Infectious Diseases (NIAID) has a long history of working to develop the live influenza vaccine and continues to support clinical studies using FluMist. The timeline below shows FluMist's developmental milestones and its progress toward approval by the Food and Drug Administration.

Hitching a Ride: New Delivery System Gets
Flu Antigen Where It Needs to Go

With vaccines-flu or otherwise-sometimes getting there is half the battle. William Ernst, Ph.D., director of molecular biology and formulations at Molecular Express, Los Angeles, CA, thinks he's found a better ride.

Dr. Ernst and colleagues have developed a vaccine delivery system that makes use of small synthetic vesicles, called liposomes, to transport flu antigens into the body. A liposome's fatty outer layer is similar to a cell's outer layer. When the virus-sized liposome meets up with its designated cell, it merges with the cell, emptying its contents inside. Although drug companies have used liposomes for decades to transport drugs housed within them into cells and tissues, Dr. Ernst is adding an upgrade. He's combining liposome technology with recombinant gene technology to create a liposome that carries the business end of the M2 protein protruding from its surface. When the body's immune system spots the M2 protein now sticking from a cell's surface, it begins making antibodies against it.

"Vaccines made from whole viruses can cause serious side effects," says Dr. Ernst, "which is why we wanted to limit our vaccine to one antigen-and, more specifically, to one key segment of that antigen. We chose the M2 protein because it's less prone to mutate, and it could help initiate an immune response in a pandemic."

To create the M2-bearing liposome, the researchers position the M2 gene in front of a gene encoding a specially designed protein that doesn't mix with water (hydrophobic). Once this recombinant gene is delivered inside of a bacterium, it drives the expression of a fusion protein, which contains the protein sequences of both the M2 and the hydrophobic protein. When the resulting fusion protein is introduced to a liposome, the protein's water-hating side will preferentially insert itself into the liposome bilayer, causing the M2 protein to protrude from it.

Currently, Dr. Ernst and others are testing how well the M2 liposome vaccine fares in protecting mice against two potentially pandemic strains of influenza, including H5N1 and H9N2, as well as endemic strains. They are also testing which works better: an injection administered under the skin or into the nasal cavity. The researchers published their findings in the journal Vaccine in 2006.

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.