Comstedt Pär, Schüler Wolfgang, Meinke Andreas, Lundberg Urban
Valneva Austria GmbH, Vienna, Austria.
PLoS One. 2017 Sep 1;12(9):e0184357. doi: 10.1371/journal.pone.0184357. eCollection 2017.
We have previously shown that the Outer surface protein A (OspA) based Lyme borreliosis vaccine VLA15 induces protective immunity in mice. Herein, we report the induction of protective immunity by VLA15 with mouse models using ticks infected with B. burgdorferi (OspA serotype 1), B. afzelii (OspA serotype 2) and B. bavariensis (OspA serotype 4) or with in vitro grown B. garinii (OspA serotype 5 and 6) for challenge. For B. garinii (OspA serotype 3), we have developed a growth inhibition assay using chicken complement and functional antibodies targeting B. garinii (OspA serotype 3) could be demonstrated after immunization with VLA15. Furthermore, following three priming immunizations, a booster dose was administered five months later and the induction of immunological memory could be confirmed. Thus, the antibody titers after the booster dose were increased considerably compared to those after primary immunization. In addition, the half-lives of anti-OspA serotype specific antibodies after administration of the booster immunization were longer than after primary immunization. Taken together, we could show that VLA15 induced protection in mice against challenge with four different clinically relevant Borrelia species (B. burgdorferi, B. afzelii, B. garinii and B. bavariensis) expressing five of the six OspA serotypes included in the vaccine. The protection data is supported by functional assays showing efficacy against spirochetes expressing any of the six OspA serotypes (1 to 6). To our knowledge, this is the first time a Lyme borreliosis vaccine has been able to demonstrate such broad protection in preclinical studies. These new data provide further promise for the clinical development of VLA15 and supports our efforts to provide a new Lyme borreliosis vaccine available for global use.
我们之前已经表明，基于外表面蛋白A（OspA）的莱姆病疫苗VLA15可在小鼠中诱导保护性免疫。在此，我们报告了使用感染伯氏疏螺旋体（OspA血清型1）、阿氏疏螺旋体（OspA血清型2）和巴伐利亚疏螺旋体（OspA血清型4）的蜱或体外培养的加氏疏螺旋体（OspA血清型5和6）进行攻毒的小鼠模型中，VLA15诱导的保护性免疫。对于加氏疏螺旋体（OspA血清型3），我们开发了一种使用鸡补体的生长抑制试验，并且在用VLA15免疫后可以证明针对加氏疏螺旋体（OspA血清型3）的功能性抗体。此外，在进行三次初次免疫后，五个月后给予加强剂量，并且可以确认免疫记忆的诱导。因此，与初次免疫后相比，加强剂量后的抗体滴度显著增加。此外，加强免疫后抗OspA血清型特异性抗体的半衰期比初次免疫后更长。综上所述，我们可以表明VLA15在小鼠中诱导了针对表达疫苗中包含的六种OspA血清型中的五种的四种不同临床相关疏螺旋体物种（伯氏疏螺旋体、阿氏疏螺旋体、加氏疏螺旋体和巴伐利亚疏螺旋体）攻毒的保护作用。功能试验支持了保护数据，显示对表达六种OspA血清型（1至6）中任何一种的螺旋体有效。据我们所知，这是莱姆病疫苗首次能够在临床前研究中证明如此广泛的保护作用。这些新数据为VLA15的临床开发提供了进一步的希望，并支持我们努力提供一种可供全球使用的新型莱姆病疫苗。
