Generation of human antibody fragments against Streptococcus mutans using a phage display chain shuffling approach.
BACKGROUND
Common oral diseases and dental caries can be prevented effectively by passive immunization. In humans, passive immunotherapy may require the use of humanized or human antibodies to prevent adverse immune responses against murine epitopes. Therefore we generated human single chain and diabody antibody derivatives based on the binding characteristics of the murine monoclonal antibody Guy's 13. The murine form of this antibody has been used successfully to prevent Streptococcus mutans colonization and the development of dental caries in non-human primates, and to prevent bacterial colonization in human clinical trials.


RESULTS
The antibody derivatives were generated using a chain-shuffling approach based on human antibody variable gene phage-display libraries. Like the parent antibody, these derivatives bound specifically to SAI/II, the surface adhesin of the oral pathogen S. mutans.


CONCLUSIONS
Humanization of murine antibodies can be easily achieved using phage display libraries. The human antibody fragments bind the antigen as well as the causative agent of dental caries. In addition the human diabody derivative is capable of aggregating S. mutans in vitro, making it a useful candidate passive immunotherapeutic agent for oral diseases.
Kuepper
Michael B
MB
Fraunhofer Institute for Molecular Biology and Applied Ecology, 52074 Aachen, Germany. kuepper@molbiotech.rwth-aachen.de
Huhn
Michael
M
Spiegel
Holger
H
Ma
Julian K C
JK
Barth
Stefan
S
Fischer
Rainer
R
Finnern
Ricarda
R
D000371:Agglutination; D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000918:Antibody Specificity; D000942:Antigens, Bacterial; D001709:Biotechnology / Q000379:methods*; D003731:Dental Caries / Q000378:metabolism / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D006801:Humans; D007128:Immunoglobulin Fragments / Q000737:chemistry; D007135:Immunoglobulin Variable Region / Q000737:chemistry; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D008969:Molecular Sequence Data; D019151:Peptide Library; D013295:Streptococcus mutans / Q000235:genetics*
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D000939:Epitopes; D007128:Immunoglobulin Fragments; D007135:Immunoglobulin Variable Region; D019151:Peptide Library