Safety and immunogenicity of a recombinant Borrelia burgdorferi outer surface protein a vaccine against Lyme disease in healthy children and adolescents: A randomized controlled trial

Objective. A recombinant lipoprotein outer surface protein A (OspA) Lyme di sease (LD) vaccine (LYMErix) has been shown to be safe and effective in pre venting LD in adults and in adolescents 15 years of age and older. Children are at risk for developing LD. This clinical study was conducted to addres s the safety and immunogenicity of LD vaccine in children 4 to 18 years of age. Methods. A randomized, placebo-controlled clinical trial was conducted at 1 7 investigational sites in Lyme-endemic areas in the United States. Immunog enicity data from this study also were compared with data obtained from the adult efficacy study. A total of 4090 healthy children and adolescents (ag e range: 4-18; mean age: 10.4 years) were randomized; 4087 were vaccinated, and a subset of 301 children participated in the immunogenicity analysis. Children were randomized to receive either 30 mug of LD vaccine (N = 3063) or placebo (N = 1024) on a 0, 1, 12-month schedule. Safety assessments eval uated both solicited (local: redness, swelling, and pain; general: fever, h eadache, fatigue, arthralgia, and rash) and unsolicited adverse events. Ser um specimens were collected at month 0 or month 2, and months 6, 12, and 13 . Results. Solicited reactogenicity data revealed a higher incidence of local injection site reactions and general symptoms (fever, headache, fatigue, a nd arthralgia) in vaccine than placebo recipients. The majority of events w ere limited in duration (mean: 2-3 days) and were mild to moderate in sever ity. The total IgG anti-OspA geometric mean titer (GMT) in the pediatric va ccine recipients at month 13 was as good as and statistically higher than t he GMT in the adult cohort at month 13 (27 485 enzyme-inked immunosorbent a ssay units [EL.U]/mL vs 8216 EL.U /mL). All of the pediatric vaccine recipi ents attained a level of antibody concentration greater than or equal to 14 00 EL.U/mL (proposed seroprotective level) compared with 90% of adults atta ining levels greater than or equal to 1400 EL.U/mL in the efficacy trial. Conclusions. LD vaccine administered on a 0, 1, 12-month schedule generally is well tolerated and immunogenic in children 4 to 18 years of age. The sa fety profile consists of mild to moderate local injection site reactions an d flu-like symptoms of limited duration and did not worsen with subsequent injections. IgG GMT at month 13 was threefold higher than the month 13 GMT obtained in the adult efficacy study. This higher immune response in childr en should provide protection against LD.