Seattle researchers are addressing government concerns about viral outbreaks in the United States through the development of the flu patch. This unique method of delivering vaccinations makes healthcare more accessible to Americans and potentially people around the world.
The Infectious Disease Research Institute (IDRI), a Seattle-based nonprofit that produces diagnostic tools and vaccines to solve global health challenges, was approached to collaborate with Defense Advanced Projects Agency (DARPA) regarding a novel way to respond to the spread of infectious disease. After the global outbreak of H5N1 bird flu in 2003 and the healthcare challenges observed during the 2009 swine flu pandemic in the United States, it became clear that a new solution was necessary.
“H5 was emerging and the death toll was rising,” Darrick Carter, UW affiliate professor of medical genetics and Vice President of Adjuvant Technology at IDRI said. “They were worried what would happen if that became translated to the U.S.”
When high levels of flu activity began emerging in the United States in 2009, it was evident that a different approach for addressing infectious disease was necessary in case a more deadly virus like H5 ever emerged.
“The healthcare system was so overburdened by this mild outbreak that hospitals were on the edge of turning people away,” Carter said. “Imagine if that happened with H5.”
DARPA was looking for a way to offer vaccinations without flooding hospitals.
“The idea was to use the U.S. postal system to solve the problem,” Carter said.
A flu vaccine sent through the mail would allow many more people to have access to treatment, while simultaneously decreasing the burden on hospitals. Because of its patch format, individuals can administer it to themselves and their families without medical training.
The flu patch also takes a step forward from the traditional flu vaccine using cutting-edge developments. IDRI combined three parts for their flu patch: an antigen using virus-like particles, microneedles, and an adjuvant, a substance that enhances the immune response.
The traditional flu vaccination is made using inactivated infectious flu virus to trigger the immune system. IDRI employed a vaccine using virus-like particles from the biotechnology company Medicago.
Virus-like particles are engineered to share the same structure as viruses so the immune system can recognize them, but lack core genetic similarities making them non-infectious. Although virus-like particles also trigger the immune system, they do so in a more controlled way that limits side-effects of a stronger response like a fever or flu-like symptoms.
“You wouldn’t run a fever,” Carter said. “It is a sign your body is responding, but the key is you don’t need quite as much [of a response].”
This is a more efficient way of delivering antigens without the inconvenience associated with the immune response triggered by the inactivated infectious flu virus.
“If you think about it, the immune system resides on the surface of our skin,” Carter said.
The skin is our first source of contact with harmful bacteria we encounter. Microneedles on the patch deliver the vaccine to the intradermal space just underneath the skin instead of into the muscle like a traditional flu shot. Intradermal injection demonstrates advantages including improved immune response to the vaccine.
“How many times when our ancestors were walking through the jungle did they get an injection into their muscle?” Carter asked.
Human skin is rich in antigen-presenting immune cells. This method of delivery takes advantage of that natural protective function.
The adjuvant is the final piece of the puzzle and enhances the effectiveness of a vaccine by creating a stronger immune response in the patient’s body. The goal is to trigger both the innate and adaptive immune system.
“Encoded in our DNA is the ability to recognize self and non-self,” Carter said. “If there are certain triggers of the innate immune system, then the body thinks there’s something going on there and responds.”
The innate immune system is the first line of defense. By effectively engaging the innate immune response, adaptive immunity is improved as well. The adaptive immune system more effectively targets the pathogen and creates an immune memory. In the future, the body will have a swift response if it ever encounters the same infection again.
Twice a year, the World Health Organization (WHO) makes recommendations onwhat strains of inactivated virus should be included in the flu vaccine based on surveillance data and forecasting about which viruses are most likely to circulate. If a drifted version of the virus is encountered, the efficacy of the vaccine will be greatly reduced.
“If we can broaden the immune response, we can protect more people,” Carter said.
The flu patch demonstrates promise for a broadened immune response that inhibits viruses not present in the vaccine. Carter cited findings that IDRI’s improved vaccine could protect over 40 percent of people from a drifted virus and 15 percent of people from a virus from a different clade.
Looking forward, this technology offers IDRI new avenues through which to continue addressing global health issues.
The continuing shortage of trained health workers in low and middle-income countries is a pressing concern. There were an estimated 13 physicians per 100,000 people in Africa compared to 280 physicians per 100,000 people in North America in 2004. Vaccines produced in this patch format increase accessibility in settings with health worker shortages because there is no special medical training or knowledge required to apply the patch.
IDRI is also exploring applications in cancer immunology. Cancer immunology trains the immune system to recognize and attack tumors the same way vaccines train the body to recognize and attack viral infections.
