Scientists at the School of Medicine have developed a new method to track how efficiently vaccines are delivered to the body. Previously it was often unclear how a vaccine injection worked in the body and whether it was doing what it was intended to do.
The Hopkins team has developed the first effective and noninvasive method to track the vaccine particles as they travel through your body to induce immunity. This may be a valuable tool in the development and evaluation of new vaccines for infectious diseases and cancer.
Vaccines are comprised of proteins or other particles that mimic the bacterium or virus that causes a disease. For instance, the flu vaccine contains weakened or killed flu virus to stimulate your immune system to respond to actual, live flu virus. However, the process of vaccination is plagued by low efficiency and variability.
"The proteins that you inject have to be captured and gobbled up by cells called antigen-presenting cells, which need to leave the skin or muscle and find their way to lymph nodes," Hyam Levitsky, a professor in the Department of Oncology and one of the scientists who led the study, said.
At the lymph nodes, antigen-presenting cells stimulate white blood cells called B cells and T cells to make antibodies and mount other responses, cumulating in a successful defense against disease.
"As few as 10 percent of cells that capture the antigen make it into the lymph node," Levitsky said. "There's sort of a bottleneck, and if you can make more cells go to lymph nodes, you get a stronger immune response." Additionally, responses to the vaccine can vary greatly between patients.
In one experiment, researchers injected genetically identical mice with an identical vaccine. With all other conditions the same, there was significant variability in the amount of antigen that made it to the lymph nodes. The variability obviously becomes much greater with individual human patients.
Previously, if scientists wanted to track the path of a vaccine through blood and lymph, they had to extract cells from the test subject, label them and inject them back into the test subject to track their path through the body.
The Hopkins team has found that they can use a commercially available iron compound, currently used to image the liver during magnetic resonance imaging (MRI), to noninvasively track vaccine delivery.
Before injecting the vaccine, it is tagged with submicroscopic iron particles. After several days, MRI allows scientists to quantify the amount of iron that has migrated to the lymph nodes, representing the amount of vaccine successfully delivered.
"This is the first time anyone has been able to visualize antigen capture and delivery in a quantifiable way. We think this will have tremendous utility in the development of new vaccines and adjuvants," Levitsky said. Adjuvents are compounds injected along with the vaccine that activate more antigen-presenting cells to travel to lymph nodes.
The study was conducted in collaboration with Jeff Bulte, a professor in the Department of Radiology. The research team focused their work on cancer vaccines, which are currently not approved for use in the United States. "There is no reason this technology can't be applied to other vaccines," Levitsky said.
He believes the method will be very useful in further developing malaria and tuberculosis vaccines, as well as developing more effective adjuvants for other vaccines.
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