Journal Article Research Support, N.I.H., Extramural Ppublish 3 citations
PubMed: 38470113 DOI: 10.1128/iai.00084-24
Single-domain antibodies reveal unique borrelicidal epitopes on the Lyme disease vaccine antigen, outer surface protein A (OspA).
Infect Immun 92(4):e0008424
Authors: David J Vance, Saiful Basir, Carol Lyn Piazza, Graham G Willsey, H M Emranul Haque, Jacque M Tremblay, Michael J Rudolph, Beatrice Muriuki, Lisa Cavacini, David D Weis, Charles B Shoemaker, Nicholas J Mantis
Affiliations
- Division of Infectious Diseases, New York State Department of Health, Wadsworth Center, Albany, New York, USA.
- Department of Biomedical Sciences, University at Albany, Albany, New York, USA.
- Department of Chemistry, The University of Kansas, Lawrence, Kansas, USA.
- Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, USA.
- New York Structural Biology Center, New York, New York, USA.
- Department of Medicine, University of Massachusetts Chan School of Medicine, Worcester, Massachusetts, USA.
Abstract
Camelid-derived, single-domain antibodies (VHs) have proven to be extremely powerful tools in defining the antigenic landscape of immunologically heterogeneous surface proteins. In this report, we generated a phage-displayed VH library directed against the candidate Lyme disease vaccine antigen, outer surface protein A (OspA). Two alpacas were immunized with recombinant OspA serotype 1 from strain B31, in combination with the canine vaccine RECOMBITEK Lyme containing lipidated OspA. The phage library was subjected to two rounds of affinity enrichment ("panning") against recombinant OspA, yielding 21 unique VHs within two epitope bins, as determined through competition enzyme linked immunosorbent assays (ELISAs) with a panel of OspA-specific human monoclonal antibodies. Epitope refinement was conducted by hydrogen exchange-mass spectrometry. Six of the monovalent VHs were expressed as human IgG1-Fc fusion proteins and shown to have functional properties associated with protective human monoclonal antibodies, including agglutination, outer membrane damage, and complement-dependent borreliacidal activity. The VHs displayed unique reactivity profiles with the seven OspA serotypes associated with genospecies in the United States and Europe consistent with there being unique epitopes across OspA serotypes that should be considered when designing and evaluating multivalent Lyme disease vaccines.
MeSH
Lyme Disease Vaccines, Immunity, Epitopes, Infections, Libraries, Membrane Proteins, Antibodies, Monoclonal, Bacteriophages, Staphylococcal Protein A, Single-Domain Antibodies