Safety and immunogenicity profile of a recombinant outer-surface protein A Lyme disease vaccine: clinical trial of a 3-dose schedule at 0, 1, and 2 months.
OBJECTIVE
This study compared the tolerability of a Lyme disease vaccine administered intramuscularly at 0 and 1 months with that of a vaccine administered at 0, 1, and 2 months to determine (1) whether adding a third dose of vaccine 1 month after the second would affect the safety profile, and (2) whether a shortened vaccination schedule of 0, 1, and 2 months would provide an immune response similar to that obtained with vaccine administered at 0, 1, and 12 months.


BACKGROUND
An efficacy trial of a Lyme disease vaccine had demonstrated safety and efficacy against definite (clinically manifested and laboratory-confirmed) Lyme disease after 3 doses at 0, 1, and 12 months and resulted in 90% of subjects having titers > or =1400 enzyme-linked immunosorbent assay units (EL.U)/mL (the proposed seroprotective level for 1 tick season).


METHODS
This multicenter, open-label, prospective, randomized study assessed the safety and efficacy of different doses of a recombinant outer-surface protein A (OspA) vaccine in 956 volunteers aged 17 to 72 years from 3 Lyme disease-endemic sites. Blood samples were collected at months 0, 2, 3, 12, and 13 to assess total immunoglobulin-G anti-OspA titers.


RESULTS
Most adverse events were transient and mild to moderate. The geometric mean antibody titer increased 2.8-fold from month 2 (1786 EL.U/mL to 4842 EL.U/mL), and approximately 90% of the volunteers had a titer > or =1400 and 99% had a titer > or =400 EL.U/mL (the mini- mum seroprotective level at any given time) after the third dose. An antibody kinetics model predicts that protection would last for a typical tick-transmission season.


CONCLUSIONS
In volunteers aged 17 to 72 years, 3 doses of vaccine administered in 2 months was well tolerated, more immunogenic than 2 doses, and provided a higher probability of protection before exposure or travel to Lyme disease-endemic areas.
Schoen
R T
RT
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8031, USA.
Sikand
V K
VK
Caldwell
M C
MC
Van Hoecke
C
C
Gillet
M
M
Buscarino
C
C
Parenti
D L
DL
D000293:Adolescent; D000328:Adult; D000368:Aged; D000954:Antigens, Surface / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001428:Bacterial Vaccines; D004334:Drug Administration Schedule; D006801:Humans; D008074:Lipoproteins; D022123:Lyme Disease Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D008875:Middle Aged; D011446:Prospective Studies; D014614:Vaccines, Synthetic / Q000276:immunology
D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D008074:Lipoproteins; D022123:Lyme Disease Vaccines; C072045:OspA protein; D014614:Vaccines, Synthetic