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Broadly conserved protective epitopes on the lyme disease vaccine antigen, OspA
by
Rudolph, Michael J.
, Mantis, Nicholas J.
, Cavacini, Lisa A.
, Chen, Yang
, Freeman-Gallant, Grace
, Piazza, Carol Lyn
, Vance, David J.
, Willsey, Graham G.
in
Analysis
/ Animals
/ Antibodies, Bacterial - immunology
/ Antibodies, Monoclonal - immunology
/ Antigenic determinants
/ Antigens, Bacterial - immunology
/ Antigens, Surface - chemistry
/ Antigens, Surface - genetics
/ Antigens, Surface - immunology
/ Bacterial Outer Membrane Proteins - chemistry
/ Bacterial Outer Membrane Proteins - genetics
/ Bacterial Outer Membrane Proteins - immunology
/ Bacterial Vaccines - immunology
/ Biology and Life Sciences
/ Borrelia burgdorferi
/ Borrelia burgdorferi - immunology
/ Care and treatment
/ Causes of
/ Computer and Information Sciences
/ Epitopes - immunology
/ Health aspects
/ Humans
/ Lipoproteins - chemistry
/ Lipoproteins - genetics
/ Lipoproteins - immunology
/ Lyme disease
/ Lyme Disease - immunology
/ Lyme Disease - prevention & control
/ Lyme Disease Vaccines - immunology
/ Medicine and Health Sciences
/ Monoclonal antibodies
/ Physical Sciences
/ Physiological aspects
/ Proteins
/ Research and Analysis Methods
2026
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Broadly conserved protective epitopes on the lyme disease vaccine antigen, OspA
by
Rudolph, Michael J.
, Mantis, Nicholas J.
, Cavacini, Lisa A.
, Chen, Yang
, Freeman-Gallant, Grace
, Piazza, Carol Lyn
, Vance, David J.
, Willsey, Graham G.
in
Analysis
/ Animals
/ Antibodies, Bacterial - immunology
/ Antibodies, Monoclonal - immunology
/ Antigenic determinants
/ Antigens, Bacterial - immunology
/ Antigens, Surface - chemistry
/ Antigens, Surface - genetics
/ Antigens, Surface - immunology
/ Bacterial Outer Membrane Proteins - chemistry
/ Bacterial Outer Membrane Proteins - genetics
/ Bacterial Outer Membrane Proteins - immunology
/ Bacterial Vaccines - immunology
/ Biology and Life Sciences
/ Borrelia burgdorferi
/ Borrelia burgdorferi - immunology
/ Care and treatment
/ Causes of
/ Computer and Information Sciences
/ Epitopes - immunology
/ Health aspects
/ Humans
/ Lipoproteins - chemistry
/ Lipoproteins - genetics
/ Lipoproteins - immunology
/ Lyme disease
/ Lyme Disease - immunology
/ Lyme Disease - prevention & control
/ Lyme Disease Vaccines - immunology
/ Medicine and Health Sciences
/ Monoclonal antibodies
/ Physical Sciences
/ Physiological aspects
/ Proteins
/ Research and Analysis Methods
2026
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Broadly conserved protective epitopes on the lyme disease vaccine antigen, OspA
by
Rudolph, Michael J.
, Mantis, Nicholas J.
, Cavacini, Lisa A.
, Chen, Yang
, Freeman-Gallant, Grace
, Piazza, Carol Lyn
, Vance, David J.
, Willsey, Graham G.
in
Analysis
/ Animals
/ Antibodies, Bacterial - immunology
/ Antibodies, Monoclonal - immunology
/ Antigenic determinants
/ Antigens, Bacterial - immunology
/ Antigens, Surface - chemistry
/ Antigens, Surface - genetics
/ Antigens, Surface - immunology
/ Bacterial Outer Membrane Proteins - chemistry
/ Bacterial Outer Membrane Proteins - genetics
/ Bacterial Outer Membrane Proteins - immunology
/ Bacterial Vaccines - immunology
/ Biology and Life Sciences
/ Borrelia burgdorferi
/ Borrelia burgdorferi - immunology
/ Care and treatment
/ Causes of
/ Computer and Information Sciences
/ Epitopes - immunology
/ Health aspects
/ Humans
/ Lipoproteins - chemistry
/ Lipoproteins - genetics
/ Lipoproteins - immunology
/ Lyme disease
/ Lyme Disease - immunology
/ Lyme Disease - prevention & control
/ Lyme Disease Vaccines - immunology
/ Medicine and Health Sciences
/ Monoclonal antibodies
/ Physical Sciences
/ Physiological aspects
/ Proteins
/ Research and Analysis Methods
2026
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Broadly conserved protective epitopes on the lyme disease vaccine antigen, OspA
Journal Article
Broadly conserved protective epitopes on the lyme disease vaccine antigen, OspA
2026
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Overview
Lyme disease, caused by the spirochete, Borrelia burgdorferi sensu latu (Bbsl), is a tickborne infection of increasing incidence in North America, Europe and Asia. While vaccines based on Outer surface protein A (OspA) have proven highly efficacious at blocking Bbsl tick-to-human transmission, the high degree of antigenic variability among the major OspA serotypes (ST) has made the development of a broadly cross protective vaccine difficult. Recent profiling of protective human monoclonal antibodies (mAbs) has suggested the existence of conserved epitopes situated within OspA’s central β-sheet (CBS), although direct comparisons of cross-serotype functionality has been hindered by biological differences among the major Bbsl genospecies. To address these issues, we developed a panel of isogenic B. burgdorferi reporter strains expressing the seven major OspA serotypes (ST1–7) and probed them with CBS-targeting mAbs to evaluate their complement-dependent borreliacidal activity. The mAbs segregated into three distinct classes: class 1 mAbs exhibited potent killing against all seven OspA serotypes, while classes 2 and 3 had restricted or no activity against two of the seven serotypes. Structural analysis of Fabs derived from each class of mAbs in complex with OspA ST1 showed that they target overlapping epitopes spanning β-strands 6–10 and involve contact with largely invariant residues. Further analysis of B. burgdorferi reporter strains expressing OspA variants from 17 additional Bbsl genospecies identified Lys-107 as a determinant of susceptibility for nearly all CBS mAbs. Taken together, these findings raise the prospect of structure-based design of a broadly protective monovalent Lyme disease vaccine.
Publisher
Public Library of Science,PLOS,Public Library of Science (PLoS)
Subject
/ Animals
/ Antibodies, Bacterial - immunology
/ Antibodies, Monoclonal - immunology
/ Antigens, Bacterial - immunology
/ Antigens, Surface - chemistry
/ Antigens, Surface - genetics
/ Antigens, Surface - immunology
/ Bacterial Outer Membrane Proteins - chemistry
/ Bacterial Outer Membrane Proteins - genetics
/ Bacterial Outer Membrane Proteins - immunology
/ Bacterial Vaccines - immunology
/ Borrelia burgdorferi - immunology
/ Computer and Information Sciences
/ Humans
/ Lyme Disease - prevention & control
/ Lyme Disease Vaccines - immunology
/ Medicine and Health Sciences
/ Proteins
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