<p>There is currently no Lyme disease (LD) vaccine available for use in humans. Outer surface protein C (OspC) of the causative agent, <i>Borrelia burgdorferi</i>, is a promising LD vaccine target. However, the extensive genetic variation of OspC poses a challenge in affording broad protection. Here, we developed a monovalent mRNA vaccine encoding OspC type A and a polyvalent vaccine encoding OspC types A, C, I, K, and N. The monovalent vaccine conferred complete protection against homologous challenge in mice, inducing functional OspC-specific antibodies and CD4⁺ T cell responses. The polyvalent formulation elicited antibodies to all encoded OspC types and protected against strains expressing OspC types A, I, and K, but not C or N. Increasing the dose enhanced protection against the OspC type C strain. This study is the first demonstration of an effective OspC-targeted mRNA vaccine and supports the development of OspC-based vaccines for broad LD prevention.</p>

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Polyvalent mRNA vaccine targeting outer surface protein C affords multi-strain protection against Lyme disease

  • Annabelle Pfeifle,
  • Casey Lansdell,
  • Wanyue Zhang,
  • Levi A. Tamming,
  • Rose Anderson-Duvall,
  • Sathya N. Thulasi Raman,
  • Caroline Gravel,
  • Jianguo Wu,
  • Grant Frahm,
  • Marybeth Creskey,
  • Maarten J. Voordouw,
  • Heather Coatsworth,
  • Weigang Qiu,
  • Richard T. Marconi,
  • Simon Sauve,
  • Lisheng Wang,
  • Xu Zhang,
  • Michael J. W. Johnston,
  • Xuguang Li

摘要

There is currently no Lyme disease (LD) vaccine available for use in humans. Outer surface protein C (OspC) of the causative agent, Borrelia burgdorferi, is a promising LD vaccine target. However, the extensive genetic variation of OspC poses a challenge in affording broad protection. Here, we developed a monovalent mRNA vaccine encoding OspC type A and a polyvalent vaccine encoding OspC types A, C, I, K, and N. The monovalent vaccine conferred complete protection against homologous challenge in mice, inducing functional OspC-specific antibodies and CD4⁺ T cell responses. The polyvalent formulation elicited antibodies to all encoded OspC types and protected against strains expressing OspC types A, I, and K, but not C or N. Increasing the dose enhanced protection against the OspC type C strain. This study is the first demonstration of an effective OspC-targeted mRNA vaccine and supports the development of OspC-based vaccines for broad LD prevention.