Although not discussed in the paper, Dr. Kolls says the vaccine approach is worth investigating its potential for offering protection against weaponized agents, such as anthrax.
In mice depleted of CD4+ T cells, which are essential for signaling other cells and for producing antigen-specific antibodies, the vaccine strategy provided protection against pneumocystis. Importantly, this vaccine strategy was able to bypass the need for T cells.
A series of experiments helped identify the two key components of the experimental DNA vaccine, so called because it has only the molecular signatures of these constructs: the molecule used by activated CD4+ T cells to signal production of antibodies, and importantly, the specific fragment of pneumocystis that receptors on these antibodies recognize.
The researchers first identified as key CD40L, a molecule expressed on activated CD4+ T cells that in turn signals other cells, including B cells, to produce antibodies against the pathogen. But antibodies rely on other cells, such as dendritic cells, to capture the antigen and advertise their bounty, which they do by displaying an antigen fragment on their cell surface. Antibodies see this antigen fragment as a mug shot of sorts, and when they recognize the same fragment expressed on the on the infecting organism the antibodies give phagocytic cells the OK to consume, or eliminate, the pathogen. Through their studies, the researchers discovered a particularly potent fragment of pneumocystis, the kexin molecule, which when isolated yielded greater antibody response than pneumocystis as a whole.
In perhaps the most significant experiments the researchers conducted, mice depleted of CD4+ T cells received the combination CD40L
Source:Children's Hospital of Pittsburgh