The novel Lyme borreliosis vaccine VLA15 shows broad protection against Borrelia species expressing six different OspA serotypes

PLoS One. 2017 Sep 1;12(9):e0184357. doi: 10.1371/journal.pone.0184357. eCollection 2017.

Abstract

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.

MeSH terms

  • Animals
  • Antibodies, Bacterial / blood
  • Antibodies, Bacterial / immunology
  • Antigens, Surface / genetics*
  • Bacterial Outer Membrane Proteins / genetics*
  • Bacterial Vaccines / genetics*
  • Borrelia burgdorferi Group / genetics*
  • Lipoproteins / genetics*
  • Lyme Disease / prevention & control*
  • Lyme Disease Vaccines / immunology*
  • Mice
  • Mice, Inbred C3H
  • Serogroup

Substances

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

Grant support

This work was funded by the Austrian Research Promotion Agency (www.ffg.at/en), BorreliaVac; grant 821824 and ZIT13 plus Technologie- und Innovationsförderungen für Wien 2013–2016, Förderprogramm Forschung, Call From Science to Products 2013. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. All authors are or were employed at Valneva Austria GmbH at the time of this work. Valneva Austria GmbH provided support in the form of salaries for authors PC, WS, AM and UL, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.”