Differential stimulation theory ruled out

A team led by Sammy Bedoui at the University of Melbourne and the Walter & Eliza Hall Institute for Medical Research, Australia, has effectively ruled out a theory for the weak boosting capacity of DNA vaccines¹.

By ‘introducing’ the immune system to proteins—or antigens—from pathogens, vaccines increase the efficiency with which immune cells called T lymphocytes respond to subsequent encounters with the same antigen.

A single injection of a DNA vaccine encoding an antigen of interest effectively induces antigen-specific T lymphocyte responses. However, a second injection with the same DNA vaccine fails to efficiently ‘boost’ the response triggered by the primary injection.

Seeking to understand the cellular basis for this weak boosting capacity, the team used mice in which dendritic cells (DC) can be ablated using a toxin and showed that DCs—one particular type of antigen presenting cell—are essential for DNA vaccine-induced T cell responses.

To determine whether DNA vaccines differentially stimulate naïve T cells, which have not previously ‘seen’ antigen, and memory T cells, which have previously ‘seen’ antigen, the researchers tracked the responses of naïve and memory antigen-specific T cells transferred into vaccinated mice. Naïve and memory T cells showed similar responses, so researchers can now focus on other possible explanations.