For the first time scientists have offered an explanation on how a common ingredient in many vaccines, provides protection against infectious diseases. The research was funded by the National Institute of Allergy and Infectious Diseases (NIAID).
The study, which appears online in the journal Nature, examines the immune system pathway and cell receptors used by alum (aluminum hydroxide/phosphate formulations), the only vaccine adjuvants licensed for general use in the United States.
Adjuvants are those substances added to a vaccine to help stimulate the immune system and make the vaccine more effective.
Vaccines must possess not only the bacterial or viral components that serve as targets of protective immune responses, but also ingredients to kick-start those immune responses.
In many vaccines, the bacterial or viral components themselves have this capability. For other vaccines, the immune system requires an added boost.
Although alum has been used to boost the immune responses to vaccines for decades, no one has known how it worked.
Many microbial compounds function as adjuvants by stimulating Toll-like receptors.
These receptors identify microbial invaders and alert the body to the presence of a disease-causing agent, or pathogen. Alum, however, does not stimulate Toll-like receptors.
The research team found that alum stimulates clusters of proteins called inflammasomes, found inside certain cells. Inflammasomes respond to stresses such as infection or injury by releasing immune cell signaling proteins called cytokines.
Inflammasomes are a component of the innate immune system that operates in parallel with, but separate from, Toll-like receptors, also part of the innate immune system.
In the study, which was led by Richard Flavell, M.D., Ph.D., and Stephanie Eisenbarth, M.D., Ph.D., the team used mice that had been genetically engineered to be deficient in various components of a specific type of inflammasome, characterized by the presence of the protein termed Nalp3.
The team demonstrated that an immune response did not occur in those animals with the deficient Nalp3 inflammasomes, despite the inclusion of alum, while it did occur in normal mice.
The team's findings provide the first convincing evidence that the Nalp3 inflammasome forms the basis for alum's adjuvant action.
According to the research team, the new information on the molecules that alum uses to activate the innate immune system should provide the keys to better understanding adjuvant function and should facilitate the design of new vaccine adjuvants.