title: An open-label, nonrandomized, single-center, prospective extension, clinical trial of booster dose schedules to assess the safety profile and immunogenicity of recombinant outer-surface protein A (OspA) Lyme disease vaccine.
abstract: BACKGROUND
  An efficacy trial of an outer-surface protein A (OspA) Lyme disease vaccine demonstrated tolerability and efficacy against laboratory-confirmed Lyme disease after a primary series of 3 doses at 0, 1, and 12 months.
  
  
  OBJECTIVE
  This extension of the efficacy study assessed the immunogenicity and tolerability of booster vaccinations administered at 24 and/or 36 months after the first vaccination.
  
  
  METHODS
  This open-label, nonrandomized, single-center, prospective extension, clinical trial was conducted in the general community in New Haven, Connecticut, where Lyme disease is endemic. Blood samples (to determine anti-OspA titer) were collected before administration of the booster doses at months 24 and 36, and at 1 and 12 months after each booster dose was administered. Immune response was assessed via total immunoglobulin G (IgG) anti-OspA antibody titers and the proportion of subjects with titers >or=1400 EL.U/mL. Adverse events (AEs) were recorded by the study volunteers on diary cards.
  
  
  RESULTS
  A total of 318 volunteers (173 women and 145 men) received at least 1 booster dose of Lyme disease vaccine, administered at 12 or 24 months after the third vaccination of the primary series (months 24 and 36, in relation to the primary series). Eighty-eight subjects of those who received a month-24 booster received a second booster dose at month 36 (12 months after the first booster). Overall, the mean age of the volunteers was 55 years (range, 19 to 73 years). The demographic characteristics of the groups were similar. Most AEs were limited induration and were rated by investigators and subjects as mild to moderate in severity. Administration of I or 2 booster doses did not elicit any patterns of AEs different from those reported in the efficacy trial. After the first booster dose, all volunteers had an anamnestic response and positive test results for total IgG antibody. Geometric mean titers increased at least 12-fold 1 month after the first booster dose at month 24 or 36. More than 96% of volunteers had titers>1400 EL.U/mL and 100% had titers >400 EL.U/mL (minimum seroprotective level) 1 month after the booster dose at month 24 or 36.
  
  
  CONCLUSIONS
  All booster doses were well tolerated, and the incidence of AEs did not increase after the second booster dose. The immune response generated after the 3-dose primary series waned; booster doses administered at 12 and/or 24 months after the primary series increased antibody levels above seroprotective levels.
authors.affiliation: Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA. Robert.Schoen@yale.edu
authors.forename: Robert T
authors.initials: RT
authors.lastname: Schoen
authors.forename: Terry
authors.initials: T
authors.lastname: Deshefy-Longhi
authors.forename: Christian
authors.initials: C
authors.lastname: Van-Hoecke
authors.forename: Charles
authors.initials: C
authors.lastname: Buscarino
authors.forename: Erol
authors.initials: E
authors.lastname: Fikrig
mesh_terms: D000328:Adult; D000368:Aged; D000954:Antigens, Surface / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001428:Bacterial Vaccines; D015748:Borrelia burgdorferi Group / Q000276:immunology; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D007074:Immunoglobulin G / Q000097:blood; D007159:Immunologic Tests; D008074:Lipoproteins; D008193:Lyme Disease / Q000276:immunology* / Q000517:prevention & control*; D022123:Lyme Disease Vaccines / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014611:Vaccination
chemical_list: D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D008074:Lipoproteins; D022123:Lyme Disease Vaccines; C072045:OspA protein