NASAL VACCINE MAY INCREASE PROTECTION AGAINST RESPIRATORY DISEASE
A vaccine administered through the nasal passages may increase protection against pneumococcal disease compared to the current vaccine, say researchers from Albany Medical College in New York and the University of Alabama at Birmingham. Their findings appear in the August 2003 issue of the journal Infection and Immunity. Streptococcus pneumoniae, a common cause of bacterial pneumonia, generally enters the body through the nose. While the current intramuscular immunizations are effective in fighting the disease, their ability to protect against bacterial carriage in the nasal passages is only fifty to sixty percent. In the study, mice were immunized intranasally, treated with interleukin-12 to enhance mucosal immune response and then challenged with varying strains of S. pneumoniae. The researchers found a seventy-five percent survival rate of vaccinated mice as opposed to a rate of zero percent in those not vaccinated. Additionally, vaccinated mice showed fewer bacterial colonies in the upper respiratory tract. "The nasal mucosa is the first point of contact for inhaled antigens, and as a consequence, intranasal immunization has emerged as potentially the most effective route of vaccination for both peripheral and mucosal immunity," say the researchers. "Intranasal vaccination may be a new approach that could be combined with standard vaccination strategies to give optimal protection both systemically and at mucosal surfaces." (J.M. Lynch, D.E. Briles, D.W. Metzger. 2003. Increased protection against pneumococcal disease by mucosal administration of conjugate vaccine plus interleukin-12. Infection and Immunity, 71. 8: 4780-4788.)
FROM BOSTON GLOBE
Can a patch replace that shot in the arm?
By Wendy Wolfson, Globe Correspondent
To the relief of terrified, shrieking toddlers and adults who still loathe getting shots, within a few years you may be able to just slap a patch on your arm to vaccinate yourself.
Iomai, a company based in Gaithersburg, Md., is developing a half-dollar-sized vaccine patch. "The name of the game with vaccines is how to deliver them to the immune system," said Dr. Gregory Glenn, the company's founder. Using "the patch is like affixing a postage stamp," he said. "The adhesive part carries the vaccine as well as sticking to the skin. When you wet the patch with water, it allows the release of the vaccine."
Unlike the transdermal patches used to deliver nicotine or contraceptives, the transcutaneous vaccine patch doesn't penetrate the skin to access the bloodstream. Instead, the vaccine patch only disrupts the outer layer of dead skin to access the immune cells that proliferate in the live skin layer beneath.
Glenn, a pediatrician, invented the vaccine patch technique in 1997 with Carl Alving, a fellow researcher at the Walter Reed Medical Army Institute of Research in Washington. That same year, he licensed the technology to found Iomai. The company is currently developing vaccine patches in partnership with pharmaceutical companies for influenza and travelers' diarrhea, and, with funding from the National Institutes of Health, for anthrax. Its vaccine patch for the flu is currently undergoing human clinical testing.
Vaccines use bits of virus, bacteria or toxins to educate the immune system to recognize and defend it from similar threats. Vaccination is nothing new. For centuries, the Turks inoculated themselves against smallpox by pricking holes in their skin and inserting scrapings from the pustules of smallpox patients. Unfortunately, the practice of scratching the skin and inserting live virus could still kill people. In 1796, Edward Jenner developed a safer method of vaccinating patients against smallpox with pus containing live virus derived from the sores of cowpox patients. Cowpox, a milder cousin to smallpox, mimicked the immune response that protected people from smallpox.
It wasn't pretty, but it saved lives.
The vaccines of our childhood were crude, too, compared with the vaccines of today. "With old vaccines, we just ground things up," Glenn said. A vaccine for "pertussis was just injected killed bacteria. The kids had side effects, but the benefits were so high, we still gave the vaccine." Vaccines made from whole-killed bacteria, which contain millions of different proteins called antigens, can trigger allergic reactions like fever and swelling. These "whole-cell" vaccines are still being used to some degree.
Modern "subunit" vaccines, such as today's hepatitis B vaccine, are considered to be "cleaner" because they contain only a specific bit of protein from the targeted virus or bacteria that has been manufactured to trigger the immune response. But, at the same time, these more precise
vaccines are often too "clean" to trigger a large-enough response in the body, so they are enhanced with immune system stimulants, called adjuvants, to make them more effective.
The immune system is extremely complex, and different methods of vaccine delivery, such as injections or patches, activate different parts of it. For example, a vaccine patch for the flu would be coated with flu virus protein and an adjuvant to stimulate the immune cells in the skin, also called Langerhans or dendritic cells. These gatekeeper cells envelop the offending proteins and escort them to the lymph nodes, triggering the creation of antibodies to fight off the disease.
For vaccines injected into the muscle, an ingredient called alum is added, which creates an inflammation to attract immune cells called macrophages to the injection site, alerting the immune system. It is this inflammation that can make your arm sore. Vaccine patches, on the other hand, are painless, though they do have to remain on your arm between one and six hours to work.
And vaccine patches could have another advantage over injectable ones. "Vaccines are usually proteins that degrade outside of refrigeration," Glenn said. If vaccines can be dried and stabilized and patches could be shipped and stored without refrigeration, this could be ideal for combat conditions, travel, or treating children in developing countries, or mass vaccinations to respond quickly to a flu epidemic.
"I think there is a need for technologies to deliver vaccines without needles," said Dr. Karen Kotloff, professor of pediatrics and medicine at the University of Maryland Center for Vaccine Development. "But the vaccine patch's full abilities still remain to be proven." Still, Kotloff sees the patch's potential. In the developing world, the problem of infections from reused needles would be lessened. And vaccine patches that do not require refrigeration could be a "tremendous asset" in tropical countries. Also, vaccine patches would help the comfort of small babies who have to undergo a number of injections all at once, she said.
Other companies are also developing vaccine patches, including Immune Focus Corp., based in Birmingham, Ala. In contrast to Iomai's approach, Immune Focus's vaccine patch is laced with a benign live virus or bacteria that carries a specific bit of the offending protein directly to the Langerhans cells in the skin to produce an immune response, said the company's chief executive officer, Dr. Charles Defesche.
Both companies readily acknowledged that FDA approval is years away. Technical issues remain, such as getting the right dosage, making sure it is properly absorbed through the skin, developing a vaccine patch stable enough to be shipped and stored, as well as meeting government regulations, which require further human clinical tests for safety, immune response, and efficacy. "All the big companies are working on this," Glenn said, "because the basic biology is so strong."