On the basis of findings by glycobiologist
Jeffrey C. Gildersleeve
of Frederick National Lab, Frederick, Md., and coworkers that humans
develop high levels of antibodies against the carbohydrate rhamnose, glycopeptide
vaccine specialist
Steven J. Sucheck of the University of Toledo
and coworkers are testing a conjugate of Tn antigen with an immune-activating peptide
called YAF and rhamnose. They are also studying multivalent conjugate vaccines made
from MUC1 glycopeptides, adjuvant, and rhamnose. A group led by
Joseph J. Barchi Jr.,
a structural glycoconjugate chemist at NCI, is developing yet another type of replacement
for carrier proteins—nanoparticles. By attaching an antibody-inducing peptide and
a MUC4 glycopeptide form of the disaccharide cancer antigen TF separately to gold
nanoparticles, Barchi and coworkers have been able to raise antibodies that recognize
both TF and the TF-glycopeptides. “I wanted to see if you could create immunity
on a nanocarrier like gold and at the same time go against the paradigm of needing
to covalently conjugate carbohydrate antigens to carrier proteins like KLH,†Barchi
says. However, immune responses induced by the conjugates have so far been weak
and nonprotective, he notes. His team continues to optimize the conjugates’ construction
in hopes of boosting the immune response to them.