Vaccines are a weakened or deactivated copy of a virus, injected to stimulate the body’s immune response to a that specific virus. Additional substances, called adjuvants, are added to the vaccine to boost its efficiency. Currently, these adjuvants do not travel well through the lymph system, remaining at the injection site where they trigger an inflammatory response from mast cells in the skin. This mode of activation could be be much more effective if the particles could travel to the lymph nodes.
In the normal course of immune response, mast cells in the body produce granules that contain a chemical called tumor necrosis factor (TNF). These granules deposit TNF as well as other immune-response “mediators” that wait for an infecting pathogen to attack. The Duke team’s goal was to develop a synthetic adjuvant that could mimic these granules and deliver them immediately to the lymph nodes, speeding immune responses when combined with the vaccine.
To test their hypothesis, researchers engineered granules made of a carbohydrate backbone containing tiny capsules of TNF. They vaccinated mice with a vaccine for influenza A that was enhanced with the granules, then infected the mice with a lethal dose of the virus. The mice showed a stronger immune response and better survival rates compared to mice that did not receive the new adjuvant. Additionally, researchers found that they could further engineer the granules, adding a cytokine called IL-12, creating an even more specialized immune response to infection.
Armed with these findings, the Duke University team is poised to take new steps toward applying them in humans, paving the way for future development of unique, medically-personalized vaccines.
Supporting references for this study may be found here: