Evolutionary phage peptide library yields Cryptococcus vaccine.

2003 FEB 12 - (NewsRx.com & NewsRx.net) -- "Cryptococcus neoformans causes a life-threatening meningoencephalitis in a significant percentage of AIDS patients," according to a study from the Albert Einstein College of Medicine in New York City.

"Mice immunized with a glycoconjugate vaccine composed of the glucuronoxylomannan (GXM) component of the cryptococcal capsular polysaccharide conjugated to tetanus toxoid (TT) produce Abs that, based on the epitope recognized, can be either protective or nonprotective. Since nonprotective Abs block the efficacy of protective Abs, we are interested in developing a vaccine that would focus the immune response specifically to protective epitopes," explained D.O. Beenhouwer and coauthors.

"Previously, we screened a phage display library with 2H1, a protective anti-GXM mAb, and isolated PAI, a representative peptide that had a kDa of 295 nM for 2H1. Mice immunized with PAI conjugated to keyhole limpet hemocyanin developed high antipeptide (1113,000), but low anti-GXM (maximum, 1/200) titers," Beenhouwer and colleagues wrote. "We now report our efforts to improve this vaccine by screening a sublibrary with six random amino acids added to either end of the PA1 motif to identify higher affinity peptides."

"P206.1, a peptide isolated from this sublibrary, had 80-fold higher affinity for 2HI (kDa=3.7 nM) than PAL. P206.1 bound protective, but not ...