Anti-OspA DNA-Encoded Monoclonal Antibody Prevents Transmission of Spirochetes in Tick Challenge Providing Sterilizing Immunity in Mice

J Infect Dis. 2019 Mar 15;219(7):1146-1150. doi: 10.1093/infdis/jiy627.

Abstract

We recently developed anti-OspA human immunoglobulin G1 monoclonal antibodies (HuMAbs) that are effective in preventing Borrelia transmission from ticks in a murine model. Here, we investigated a novel approach of DNA-mediated gene transfer of HuMAbs that provide protection against Lyme disease. Plasmid DNA-encoded anti-OspA HuMAbs inoculated in mice achieved a serum antibody concentration of >6 μg/mL. Among mice injected with DNA-encoded monoclonal antibodies, 75%-77% were protected against an acute challenge by Borrelia-infected ticks. Our results represent the first demonstration of employing DNA transfer as a delivery system for antibodies that block transmission of Borrelia in animal models.

Keywords: DMAb; Lyme disease; OspA; human monoclonal antibody.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / genetics
  • Antibodies, Monoclonal, Humanized / immunology*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antigens, Surface / genetics
  • Antigens, Surface / immunology*
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / immunology*
  • Bacterial Vaccines / genetics
  • Bacterial Vaccines / immunology*
  • Borrelia burgdorferi
  • DNA, Bacterial / immunology*
  • Female
  • HEK293 Cells
  • Humans
  • Lipoproteins / genetics
  • Lipoproteins / immunology*
  • Lyme Disease / prevention & control
  • Lyme Disease / transmission*
  • Mice
  • Mice, Inbred C3H
  • Mice, SCID
  • Plasmids / immunology
  • Ticks
  • Transfection

Substances

  • Antibodies, Monoclonal, Humanized
  • Antigens, Surface
  • Bacterial Outer Membrane Proteins
  • Bacterial Vaccines
  • DNA, Bacterial
  • Lipoproteins
  • OspA protein