- 作者：Nina Wressnigg ; Eva-Maria P?llabauer ; Gerald Aichinger ; Daniel Portsmouth ; Alex ; ra L?w-Baselli ; S ; or Fritsch ; Ian Livey ; Brian A Crowe ; Michael Schwendinger ; Peter Br¨¹hl ; Andreas Pilz ; Thomas Dvorak ; Julia Singer ; Clair Firth ; Benjamin Luft ; Bernhard Schmitt ; Markus Zeitlinger ; Markus M¨¹ller ; Herwig Kollaritsch ; Maria Paulke-Korinek ; et al.
- 刊名：The Lancet Infectious Diseases
- 出版年：2013
- 出版时间：August, 2013
- 年：2013
- 卷：13
- 期：8
- 页码：680-689
- 全文大小：256 K
Summary
Background
Lyme borreliosis is caused by Borrelia burgdorferi sensu stricto in the USA and by several Borrelia species in Europe and Asia, but no human vaccine is available. We investigated the safety and immunogenicity of adjuvanted and non-adjuvanted vaccines containing protective epitopes from Borrelia species outer surface protein A (OspA) serotypes in healthy adults.Methods
Between March 1, 2011, and May 8, 2012, we did a double-blind, randomised, dose-escalation phase 1/2 study at four sites in Austria and Germany. Healthy adults aged 18-70 years who were seronegative for B burgdorferi sensu lato were eligible for inclusion. Participants were recruited sequentially and randomly assigned to one of six study groups in equal ratios via an electronic data capture system. Participants and investigators were masked to group allocation. Participants received three vaccinations containing 30 ¦Ìg, 60 ¦Ìg, or 90 ¦Ìg OspA antigen with or without an adjuvant, with intervals of 28 days, and a booster 9-12 months after the first immunisation. The coprimary endpoints were the frequency and severity of injection-site and systemic reactions within 7 days of each vaccination, and the antibody responses to OspA serotypes 1-6, as established by ELISA. This study is registered with , number .
Findings
300 participants were randomly assigned: 151 to adjuvanted vaccines (50 to 30 ¦Ìg, 51 to 60 ¦Ìg, and 50 to 90 ¦Ìg doses), and 149 to non-adjuvanted vaccines (50 to 30 ¦Ìg, 49 to 60 ¦Ìg, and 50 to 90 ¦Ìg doses). Adverse reactions were predominantly mild, and no vaccine-related serious adverse events were reported. The risk of systemic reactions (risk ratio 0¡¤54 [95 % CI 0¡¤41-0¡¤70]; p<0¡¤0001) and of moderate or severe systemic reactions (0¡¤35 [0¡¤13-0¡¤92]; p=0¡¤034) was significantly lower for adjuvanted than non-adjuvanted formulations. The 30 ¦Ìg adjuvanted formulation had the best tolerability profile; only headache (five [10 % , 95 % CI 4-20] of 50), injection-site pain (16 [32 % , 21-45]), and tenderness (17 [34 % , 23-47]) affected more than 6 % of patients. All doses and formulations induced substantial mean IgG antibody titres against OspA serotypes 1-6 after the first three vaccinations (range 6944-17?321) and booster (19?056-32?824) immunisations. The 30 ¦Ìg adjuvanted formulation induced the highest antibody titres after the booster: range 26?143 (95 % CI 18?906-36?151) to 42?381 (31?288-57?407).
Interpretation
The novel multivalent OspA vaccine could be an effective intervention for prevention of Lyme borreliosis in Europe and the USA, and possibly worldwide. Larger confirmatory formulation studies will need to be done that include individuals seropositive for Borrelia burgdorferi sensu lato before placebo-controlled phase 3 efficacy studies can begin.
Funding
Baxter.