Synthetic peptides corresponding to protective epitopes of Escherichia coli digalactoside-binding pilin prevent infection in a murine pyelonephritis model.

Abstract

Synthetic peptides corresponding to five segments of a globoside (Gal-Gal)-binding pilin sequence [residues 5-12 (R5-12), R65-75, R93-104, R103-116, and R131-143], cyanogen bromide fragment II (CNBr-II, R53-163), and purified, intact Gal-Gal pili were prepared as vaccines and tested for their efficacy in a BALB/c murine model of pyelonephritis. Intact Gal-Gal pili, CNBr-II, and synthetic peptides R5-12 and R65-75 engendered antibodies that bound the homologous pilin protein and prevented urine and renal colonization in most vaccine recipients. Protection correlated with serum anti-pilus IgG ELISA titers greater than or equal to 1:250. The efficacy afforded by synthetic peptides R5-12 and R65-75 in vaccinated mice indicates that linear "antigenic" determinants in separate cyanogen bromide fragments encode "protective" epitopes. Peptides R93-104, R103-116, and R131-143 lacked efficacy, indicating that not all regions of the sequence are serologically equivalent. The crossreactivity of the peptide antisera for different Gal-Gal pilins was also assessed and correlated with the sequence homology of the corresponding regions. Antiserum to peptide R65-75, which corresponds to a region of unconserved sequence in heterologous pilins, bound only the homologous pilin. Thus, it specifies a type-specific protective epitope. Antiserum to synthetic peptide R5-12, which corresponds to a region of conserved sequence, bound Gal-Gal pilins from seven of eight pyelonephritis strains, indicating that it specifies a crossreacting protective epitope.

• Authors: M A Schmidt, P O'Hanley, D Lark, G K Schoolnik
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 85 Issue 4 Pg. 1247-51 (Feb 1988) ISSN: 0027-8424 [Print] United States
• PMID: 2448796 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Bacterial
• Bacterial Outer Membrane Proteins
• Bacterial Vaccines
• Epitopes
• Peptide Fragments
• Fimbriae Proteins
• Galactose

Topics

• Animals
• Antibodies, Bacterial (immunology)
• Bacterial Outer Membrane Proteins (immunology, metabolism, pharmacology)
• Bacterial Vaccines (immunology)
• Cross Reactions
• Epitopes (immunology)
• Escherichia coli (immunology)
• Escherichia coli Infections (prevention & control)
• Female
• Fimbriae Proteins
• Galactose (metabolism)
• Mice
• Mice, Inbred BALB C
• Peptide Fragments (chemical synthesis, immunology, pharmacology)
• Pyelonephritis (prevention & control)