The Factor H-Binding Site of CspZ as a Protective Target against Multistrain, Tick-Transmitted Lyme Disease

Infect Immun. 2020 Apr 20;88(5):e00956-19. doi: 10.1128/IAI.00956-19. Print 2020 Apr 20.

Abstract

The spirochete Borrelia burgdorferi sensu lato is the causative agent of Lyme disease (LD). The spirochetes produce the CspZ protein that binds to a complement regulator, factor H (FH). Such binding downregulates activation of host complement to facilitate spirochete evasion of complement killing. However, vaccination with CspZ does not protect against LD infection. In this study, we demonstrated that immunization with CspZ-YA, a CspZ mutant protein with no FH-binding activity, protected mice from infection by several spirochete genotypes introduced via tick feeding. We found that the sera from CspZ-YA-vaccinated mice more efficiently eliminated spirochetes and blocked CspZ FH-binding activity than sera from CspZ-immunized mice. We also found that vaccination with CspZ, but not CspZ-YA, triggered the production of anti-FH antibodies, justifying CspZ-YA as an LD vaccine candidate. The mechanistic and efficacy information derived from this study provides insights into the development of a CspZ-based LD vaccine.

Keywords: Borrelia; CspZ; Lyme disease; vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies / immunology
  • Bacterial Proteins / immunology*
  • Binding Sites / immunology
  • Borrelia burgdorferi / immunology*
  • Complement Factor H / immunology*
  • Complement System Proteins / immunology
  • Female
  • Humans
  • Lyme Disease / immunology*
  • Lyme Disease Vaccines / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Ticks / microbiology*

Substances

  • Antibodies
  • Bacterial Proteins
  • Lyme Disease Vaccines
  • Complement Factor H
  • Complement System Proteins