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Vaccine adjuvant uses host DNA to boost pathogen recognition
Date:4/5/2013

reveal the role that DNA plays.

The National Jewish Health team had previously shown that the process starts with a series of events similar to those that initiate responses to bacterial infections. Neutrophils, and other early responders in the immune system, flood into a site of potential infection, attack the foreign agent, in this case the alum vaccine, then quickly die in massive numbers.

Upon death the neutrophils release large amounts of DNA, which uncoils from its chromatin spools and acts somewhat like a net to entangle the foreign agent. Other cells then engulf the DNA-alum-vaccine complex. These antigen-presenting cells display small fragments of the vaccine on their surfaces for T-cells to recognize. T-cells drive the adaptive immune response, the one that recognizes and attacks the specific infectious agent, as opposed to the more general innate immune response.

T-cells are also the basis for effective vaccines. Some T-cells, and the B-cells stimulated by the T-cells, transform into memory cells once the infection has been cleared. Those memory cells help mount a quicker and stronger immune response if they see that organism again.

The National Jewish Health team showed that the DNA coating the adjuvant doubles the time that the T-cell engages the vaccine fragment on the surface of the antigen-presenting cell. When they added DNase to digest DNA, the T-cell engaged the vaccine fragment half as long, and the vaccine was less effective. Several of the findings were made possible by an innovative use of multi-photon microscopy to film the interaction of T-cells and antigen-presenting cells.

"The DNA makes the antigen-presenting cell stickier," said Amy McKee, PhD, Instructor at the University of Colorado, and lead author of the paper. "We believe that extended engagement provides a stronger signal to the T-cell, which makes the immune response more robust."

The researchers are not sure exactly what makes the antigen-presenting cel
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Contact: William Allstetter
allstetterw@njhealth.org
303-398-1002
National Jewish Health
Source:Eurekalert

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