Safety and immunogenicity profile of a recombinant outer-surface protein ALyme disease vaccine: Clinical trial of a 3-dose schedule at 0, 1, and 2 months

Objectives: This study compared the tolerability of a Lyme disease vaccine administered intramuscularly at 0 and 1 months with that of a vaccine admin istered 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 prov ide an immune response similar to that obtained with vaccine administered a t 0, 1, and 12 months. Background: An efficacy trial of a Lyme disease vaccine had demonstrated sa fety and efficacy against definite (clinically manifested and laboratory-co nfirmed) Lyme disease after 3 doses at 0, 1, and 12 months and resulted in 90% of subjects having titers greater than or equal to 1400 enzyme-linked i mmunosorbent assay units (EL.U)/mL (the proposed seroprotective level for 1 rick season). Methods: This multicenter, open-label, prospective, randomized study assess ed the safety and efficacy of different doses of a recombinant outer-surfac e protein A (OspA) vaccine in 956 volunteers aged 17 to 72 years from 3 Lym e disease-endemic sites. Blood samples were collected at months 0, 2, 3, 12 , and 13 to assess total immunoglobulin-a anti-OspA titers. Results: Most adverse events were transient and mild to moderate. The,geome tric mean antibody titer increased 2.8-fold from month 2 (1786 EL.U/mL to 4 842 EL.U/mL), and similar to 90% of the volunteers had a titer greater than or equal to 1400 and 99% had a titer greater than or equal to 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 typic al tick-transmission season. Conclusions: In volunteers aged 17 to 72 years, 3 doses of vaccine administ ered in 2 months was well tolerated, more immunogenic than 2 doses, and pro vided a higher probability of protection before exposure or travel to Lyme disease-endemic areas.