June 12, 2005
Finding Speeds up Immunization Booster Schedule
Parents often wonder why it takes a year or more and multiple shots to fully immunize their children against diseases like diphtheria and pertussis. The reason is twofold. First, a single vaccination generates only a small amount of immunity and booster shots are needed to build up immunity to protective levels. The second reason is due to the fact that a substantial "lag time" is required by the immune system between initial immunization and subsequent booster shots to maximize the size of each boost.
Researchers at the University of Iowa Roy J. and Lucille A Carver College of Medicine have discovered that a different vaccination strategy, called dendritic cell vaccination, can dramatically speed up the immunization process by greatly reducing the required "lag time" between the initial vaccination and the booster shots. The finding has important implications for immunotherapy -- using vaccines to treat cancer -- where developing immunity fast is critical.
In the UI study, mice treated with a dendritic cell vaccine and a booster shot were protected against a bacterial infection in a matter of days compared to the several weeks required by normal vaccination to generate immunity. The study results appeared in Nature Medicine advance online publication (AOP) at the journal's Web site (http://www.nature.com/nm/index.html) on June 12.
"People should not be concerned that vaccines don't work -- if you have plenty of time, current vaccine and booster regimens work very well," said John Harty, Ph.D., UI professor of microbiology in the Carver College of Medicine, and senior author of the study. "But there are circumstances, such as using a vaccine to treat a fast-growing cancer, where the immune response might be needed much more rapidly. With the dendritic cell vaccinations, we really speed up the booster schedule and also speed up the time it takes to achieve protective immunity."
Harty, who also is the Carver College of Medicine Endowed Professor in Microbial Immunology, noted that there already are DC vaccines in clinical trials for cancer, and if the new information from the UI study can be applied in humans, then the findings might provide a way to greatly speed up the booster schedule for immunotherapies and shorten the time needed to generate protective immunity.
Dendritic cells (DCs) are an important component of the immune system. They act like scouts, monitoring the body for foreign invaders such as bacteria or viruses. Contact with the invading microbe "arms" the dendritic cells, which then travel from the infection site to the lymph nodes where they activate specific T cells. These stimulated T cells proliferate and go through a transformation process, first becoming effector cells that can fight the infection and then developing memory characteristics, which are the basis of long-term immunity against that infection.
This T cell transformation process takes time, and only memory T cells can proliferate in response to a booster vaccination or a second infection. Thus it is necessary to allow for this "lag time," in which the memory T cell population develops, before giving a booster shot designed to bump up immunity.
The DC vaccination strategy used by Harty and his colleagues involved "arming" dendritic cells against a specific bacterium in a petri dish and then immunizing mice with the altered dendritic cells. The UI team found that these DC vaccinations cause an accelerated production of memory T cells.
"Six days after infection or conventional immunization those memory cells are not yet available to be expanded by the booster shot. But six days after a DC vaccination they are," Harty said. "An initial DC vaccination followed very quickly by booster shots allowed us to rapidly generate tremendous numbers of T cells."
Further experiments suggested that inflammation, which is a normal part of infection or current vaccine regimens, plays an important role in controlling the normally slow development of memory T cells. In contrast, DC vaccinations do not produce inflammation and the memory T cells develop very quickly.
"Provoking a T cell response in the absence of inflammation gives you early memory, which allows us to boost the response quickly," Harty said. "If results in humans are similar to what we see in animal models, this could represent a large step forward in vaccine efficiency, especially for situations were speedy protection is important."
In addition to Harty, the UI team included Vladimir Badovinac, Ph.D., an associate research scientist, and Kelly Messingham, Ph.D., a postdoctoral researcher, who were co-first authors of the study. Ali Jabbari and Jodie Haring, Ph.D., also were part of the research group. The study was funded by the National Institutes of Health.
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