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Biodegradable microspheres deliver time release vaccines, stimulate different immune response
March 01, 2007A new vaccine delivery system using microspheres of a biodegradable polymer may not only reduce the need for booster shots in some cases, but also appears to stimulate an immune response that traditional vaccines do not. Researchers from Iowa State University report their findings today at the ASM Biodefense and Emerging Disease Research Meeting.
"Current vaccines are good at producing antibodies that block entry into the cell. In the case of some diseases, such as malaria or tuberculosis, antibody vaccines just aren't effective," says Jenny Wilson-Welder, a lead researcher on the study.
Wilson-Welder and her colleagues initially began their research looking for a way to eliminate the need for booster vaccinations, by developing a vaccine delivery system that released the vaccine into the system slowly over time. They chose a biodegradable polymer, called polyandydride, in a microsphere formulation. This polymer was already being used as a delivery system for a brain cancer drug designed to inhibit tumor growth.
"It's like an Everlasting Gobstopper or a bar of soap. It wears away slowly over time, delivering its payload," says Wilson-Welder.
The researchers vaccinated mice with microspheres loaded with ovalbumin, a protein from chicken eggs, and measured immune reponse. While mice exhibited the expected antibody response, the researchers also noticed something unexpected. The vaccine enhanced another type of immune response known as cellular-mediated immunity (CMI). CMI allows the immune system to identify, target and kill cells that have already become infected, something antibodies can not do.
The determine the cause of this effect, Wilson-Welder and her colleagues next incubated human dendritic cells in the presence of polyanhydride microspheres (without ovalbumin). Dendritic cells are responsible for initiating CMIs.
"We observed that the polymer microspheres were activating dendritic cells," says Wilson-Welder.
The implications of these findings are two-fold, says Wilson-Welder. First, they have shown that polyanhydride microspheres can be used to deliver time-released vaccines. This could lead to the development of single-dose vaccines for diseases that currently require booster innoculations to be most effective, such as tetanus, whooping cough and chicken pox.
"The slow release mechanism of the polymers means that vaccines that currently require multiple doses might need only need a single dose in the future," says Wilson-Welder.
Secondly, the finding that vaccine adjuvants can elicit a CMI provides hope for vaccines against intracellular diseases that we currently don't have effective vaccines for, like malaria, tuberculosis and even AIDS.
"If we understand how an adjuvant activates the dendritic cells, we can start tailoring our vaccines to induce a better cellular response. If we can tailor the immune response, it holds greater promise for vaccines that we do not currently have," says Wilson-Welder.
American Society for Microbiology
"It's like an Everlasting Gobstopper or a bar of soap. It wears away slowly over time, delivering its payload," says Wilson-Welder.
The researchers vaccinated mice with microspheres loaded with ovalbumin, a protein from chicken eggs, and measured immune reponse. While mice exhibited the expected antibody response, the researchers also noticed something unexpected. The vaccine enhanced another type of immune response known as cellular-mediated immunity (CMI). CMI allows the immune system to identify, target and kill cells that have already become infected, something antibodies can not do.
The determine the cause of this effect, Wilson-Welder and her colleagues next incubated human dendritic cells in the presence of polyanhydride microspheres (without ovalbumin). Dendritic cells are responsible for initiating CMIs.
"We observed that the polymer microspheres were activating dendritic cells," says Wilson-Welder.
The implications of these findings are two-fold, says Wilson-Welder. First, they have shown that polyanhydride microspheres can be used to deliver time-released vaccines. This could lead to the development of single-dose vaccines for diseases that currently require booster innoculations to be most effective, such as tetanus, whooping cough and chicken pox.
"The slow release mechanism of the polymers means that vaccines that currently require multiple doses might need only need a single dose in the future," says Wilson-Welder.
Secondly, the finding that vaccine adjuvants can elicit a CMI provides hope for vaccines against intracellular diseases that we currently don't have effective vaccines for, like malaria, tuberculosis and even AIDS.
"If we understand how an adjuvant activates the dendritic cells, we can start tailoring our vaccines to induce a better cellular response. If we can tailor the immune response, it holds greater promise for vaccines that we do not currently have," says Wilson-Welder.
American Society for Microbiology
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