Design and development of a novel vaccine for protection against Lyme borreliosis

PLoS One. 2014 Nov 19;9(11):e113294. doi: 10.1371/journal.pone.0113294. eCollection 2014.

Abstract

There is currently no Lyme borreliosis vaccine available for humans, although it has been shown that the disease can be prevented by immunization with an OspA-based vaccine (LYMErix). Outer surface protein A (OspA) is one of the dominant antigens expressed by the spirochetes when present in a tick. The Borrelia species causing Lyme borreliosis in Europe express different OspA serotypes on their surface, B. burgdorferi (serotype 1), B. afzelii (serotype 2), B. garinii (serotypes, 3, 5 and 6) and B. bavariensis (serotype 4), while only B. burgdorferi is present in the US. In order to target all these pathogenic Borrelia species, we have designed a multivalent OspA-based vaccine. The vaccine includes three proteins, each containing the C-terminal half of two OspA serotypes linked to form a heterodimer. In order to stabilize the C-terminal fragment and thus preserve important structural epitopes at physiological temperature, disulfide bonds were introduced. The immunogenicity was increased by introduction of a lipidation signal which ensures the addition of an N-terminal lipid moiety. Three immunizations with 3.0 µg adjuvanted vaccine protected mice from a challenge with spirochetes expressing either OspA serotype 1, 2 or 5. Mice were protected against both challenge with infected ticks and in vitro grown spirochetes. Immunological analyses (ELISA, surface binding and growth inhibition) indicated that the vaccine can provide protection against the majority of Borrelia species pathogenic for humans. This article presents the approach which allows for the generation of a hexavalent vaccine that can potentially protect against a broad range of globally distributed Borrelia species causing Lyme borreliosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Surface / chemistry
  • Antigens, Surface / immunology
  • Bacterial Outer Membrane Proteins / chemical synthesis*
  • Bacterial Outer Membrane Proteins / chemistry
  • Bacterial Outer Membrane Proteins / immunology
  • Bacterial Vaccines / chemical synthesis*
  • Bacterial Vaccines / chemistry
  • Bacterial Vaccines / immunology
  • Borrelia / drug effects
  • Borrelia / immunology*
  • Disease Models, Animal
  • Epitopes / immunology
  • Female
  • Humans
  • Lipoproteins / chemical synthesis*
  • Lipoproteins / chemistry
  • Lipoproteins / immunology
  • Lyme Disease / immunology
  • Lyme Disease / prevention & control*
  • Lyme Disease Vaccines / administration & dosage
  • Lyme Disease Vaccines / chemical synthesis*
  • Mice
  • Mice, Inbred C3H
  • Ticks / microbiology

Substances

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

Grant support

This study was funded by the Austrian Research Promotion Agency (www.ffg.at/en), BorreliaVac; grant 821824. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.