LemA and Erp Y-like recombinant proteins from Leptospira interrogans protect hamsters from challenge using AddaVax™ as adjuvant

Vaccine. 2018 May 3;36(19):2574-2580. doi: 10.1016/j.vaccine.2018.03.078. Epub 2018 Apr 3.

Abstract

Background: Recombinant subunit vaccines have been extensively evaluated as promising alternatives against leptospirosis. Here, we evaluated two proteins in formulations containing the adjuvant AddaVax™ as vaccine candidates for prevention and control of leptospirosis.

Methods: Recombinant proteins rErp Y-like and rLemA were characterized by ELISA to assess their ability to bind extracellular matrix (ECM) components and fibrinogen. Groups of eight hamsters were immunized intramuscularly with rErp Y-like or rLemA mixed with a squalene-based adjuvant (AddaVax), and then vaccine efficacy was determined in terms of protection against a lethal challenge. The humoral immune response was determined by ELISA, and the evidence of sub-lethal infection was evaluated by histopathology and kidney culture.

Results: rLemA protein binds laminin, fibrinogen, and collagen type IV, while rErp Y-like interacts with fibrinogen. Significant protection was achieved for rLemA and rErp Y-like vaccines, which showed 87.5% and 62.5% survivals, respectively. On day 28, the humoral immune response was significantly greater in the vaccine groups as compared to that in the control group, and the response was predominantly based on IgG2/3. The surviving animals showed negative results in culture isolation but presented with tissue lesions in the lungs and kidneys.

Conclusion: Cumulatively, our findings suggest that LemA and Erp Y-like proteins act as adhesins and are able to protect against mortality, but not against tissue lesions. Moreover, AddaVax is a novel adjuvant with potential for improving the immunogenicity of leptospiral vaccines.

Keywords: AddaVax; Adjuvant; Erp Y-like; LemA; Leptospirosis; Vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Vaccines / genetics
  • Bacterial Vaccines / immunology
  • Bacterial Vaccines / pharmacology*
  • Cricetinae
  • Female
  • Leptospira interrogans / genetics*
  • Leptospira interrogans / pathogenicity
  • Leptospirosis / immunology
  • Leptospirosis / prevention & control*
  • Male
  • Mice, Inbred BALB C
  • Polysorbates / pharmacology*
  • Recombinant Proteins / immunology
  • Recombinant Proteins / pharmacology
  • Squalene / pharmacology*
  • Transcription Factors / genetics
  • Vaccines, Synthetic / immunology
  • Vaccines, Synthetic / pharmacology

Substances

  • Addavax
  • Adjuvants, Immunologic
  • Bacterial Proteins
  • Bacterial Vaccines
  • Polysorbates
  • Recombinant Proteins
  • Transcription Factors
  • Vaccines, Synthetic
  • Squalene
  • lemA protein, bacterial