Identification of a defined linear epitope in the OspA protein of the Lyme disease spirochetes that elicits bactericidal antibody responses: Implications for vaccine development

• Published in: Vaccine Vol. 35; no. 24; pp. 3178 - 3185
• Main Authors: Izac, Jerilyn R, Oliver, Lee D, Earnhart, Christopher G, Marconi, Richard T
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 31.05.2017; Elsevier Limited
• Subjects: Allergy and Immunology; Amino acids; Animals; Antibodies; Antibodies, Bacterial - blood; Antigens, Bacterial - immunology; Antigens, Surface - chemistry; Antigens, Surface - genetics; Antigens, Surface - immunology; Arachnids; Arthritis; Autoimmunity; Bacterial Outer Membrane Proteins - chemistry; Bacterial Outer Membrane Proteins - genetics; Bacterial Outer Membrane Proteins - immunology; Bacterial Vaccines - chemistry; Bacterial Vaccines - genetics; Bacterial Vaccines - immunology; Bactericidal activity; Borrelia burgdorferi - chemistry; Borrelia burgdorferi - genetics; Borrelia burgdorferi - growth & development; Borrelia burgdorferi - immunology; Chimeritope; Drug Discovery; Epitopes; Epitopes - chemistry; Epitopes - immunology; Feeding; Immunization; Immunogenicity; Immunoglobulin G - blood; Immunoglobulins; Immunology; Integration; Ixodes - microbiology; Ixodes ticks; LFA-1 antigen; Lipoproteins - chemistry; Lipoproteins - genetics; Lipoproteins - immunology; Lyme disease; Lyme Disease - prevention & control; Lyme Disease Vaccines - immunology; Lyme vaccine; Mammals; Markets; Mice; Midgut; OspA protein; OspC; Outer surface protein A; Peptides - administration & dosage; Peptides - chemistry; Peptides - immunology; Polymerase Chain Reaction; Proteins; Residues; Serum Bactericidal Antibody Assay; Spirochetes; Ticks; Vaccination; Vaccine development; Vaccines; Vaccines, Subunit - administration & dosage; Vaccines, Subunit - immunology; VANGUARDcrLyme; Vector-borne diseases; Asia; United States > US; Europe; Outer surface protein A; Lyme disease; OspC; Ixodes ticks; Lyme vaccine; Chimeritope; VANGUARDcrLyme
• DOI: 10.1016/j.vaccine.2017.04.079
• ISSN: 0264-410X

Abstract The lipoprotein OspA is produced by the Lyme disease spirochetes primarily in unfed ticks. OspA production is down-regulated by the blood meal and it is not produced in mammals except for possible transient production during late stage infection in patients with Lyme arthritis. Vaccination with OspA elicits antibody (Ab) that can target spirochetes in the tick midgut during feeding and inhibit transmission to mammals. OspA was the primary component of the human LYMErix™ vaccine. LYMErix™ was available from 1998 to 2002 but then pulled from the market due to declining sales as a result of unsubstantiated concerns about vaccination induced adverse events and poor efficacy. It was postulated that a segment of OspA that shares sequence similarity with a region in human LFA-1 and may trigger putative autoimmune events. While evidence supporting such a link has not been demonstrated, most efforts to move forward with OspA as a vaccine component have sought to eliminate this region of concern. Here we identify an OspA linear epitope localized within OspA amino acid residues 221–240 (OspA221–240 ) that lacks the OspA region suggested to elicit autoimmunity. A peptide consisting of residues 221–240 was immunogenic in mice. Ab raised against OspA221–240 peptide surface labeled B. burgdorferi in IFAs and displayed potent Ab mediated-complement dependent bactericidal activity. BLAST analyses identified several variants of OspA221–240 and a closely related sequence in OspB. It is our hypothesis that integration of the OspA221–240 epitope into a multivalent-OspC based chimeric epitope based vaccine antigen (chimeritope) could result in a subunit vaccine that protects against Lyme disease through synergistic mechanisms.