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

Pediatrics. 2001 Jul;108(1):123-8. doi: 10.1542/peds.108.1.123.

Abstract

Objective: A recombinant lipoprotein outer surface protein A (OspA) Lyme disease (LD) vaccine (LYMErix) has been shown to be safe and effective in preventing 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 address 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 17 investigational sites in Lyme-endemic areas in the United States. Immunogenicity data from this study also were compared with data obtained from the adult efficacy study. A total of 4090 healthy children and adolescents (age 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 microgram of LD vaccine (N = 3063) or placebo (N = 1024) on a 0, 1, 12-month schedule. Safety assessments evaluated both solicited (local: redness, swelling, and pain; general: fever, headache, fatigue, arthralgia, and rash) and unsolicited adverse events. Serum 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, and arthralgia) in vaccine than placebo recipients. The majority of events were limited in duration (mean: 2-3 days) and were mild to moderate in severity. The total IgG anti-OspA geometric mean titer (GMT) in the pediatric vaccine recipients at month 13 was as good as and statistically higher than the GMT in the adult cohort at month 13 (27 485 enzyme-linked immunosorbent assay units [EL.U]/mL vs 8216 EL.U /mL). All of the pediatric vaccine recipients attained a level of antibody concentration >/=1400 EL.U/mL (proposed seroprotective level) compared with 90% of adults attaining levels >/=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 safety profile consists of mild to moderate local injection site reactions and 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 children should provide protection against LD.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antigens, Surface / administration & dosage
  • Antigens, Surface / adverse effects*
  • Antigens, Surface / immunology*
  • Arthralgia / chemically induced
  • Bacterial Outer Membrane Proteins / administration & dosage
  • Bacterial Outer Membrane Proteins / adverse effects*
  • Bacterial Outer Membrane Proteins / immunology*
  • Bacterial Vaccines / administration & dosage
  • Bacterial Vaccines / adverse effects*
  • Bacterial Vaccines / immunology*
  • Borrelia burgdorferi Group / immunology*
  • Child
  • Child, Preschool
  • Edema / chemically induced
  • Erythema / chemically induced
  • Exanthema / chemically induced
  • Fatigue / chemically induced
  • Female
  • Fever / chemically induced
  • Headache / chemically induced
  • Humans
  • Immunoglobulin G / blood
  • Incidence
  • Injections
  • Lipoproteins*
  • Lyme Disease / immunology
  • Lyme Disease / prevention & control*
  • Lyme Disease Vaccines / administration & dosage
  • Lyme Disease Vaccines / adverse effects*
  • Lyme Disease Vaccines / immunology*
  • Male
  • Pain / chemically induced
  • Severity of Illness Index
  • Time Factors
  • United States

Substances

  • Antigens, Surface
  • Bacterial Outer Membrane Proteins
  • Bacterial Vaccines
  • Immunoglobulin G
  • Lipoproteins
  • Lyme Disease Vaccines
  • OspA protein