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An engineered bispecific DNA-encoded IgG antibody protects against Pseudomonas aeruginosa in a pneumonia challenge model

Author

Listed:
  • Ami Patel

    (The Wistar Institute of Anatomy & Biology)

  • Antonio DiGiandomenico

    (MedImmune)

  • Ashley E. Keller

    (MedImmune)

  • Trevor R. F. Smith

    (Inovio Pharmaceuticals)

  • Daniel H. Park

    (The Wistar Institute of Anatomy & Biology)

  • Stephanie Ramos

    (Inovio Pharmaceuticals)

  • Katherine Schultheis

    (Inovio Pharmaceuticals)

  • Sarah T. C. Elliott

    (The Wistar Institute of Anatomy & Biology)

  • Janess Mendoza

    (Inovio Pharmaceuticals)

  • Kate E. Broderick

    (Inovio Pharmaceuticals)

  • Megan C. Wise

    (The Wistar Institute of Anatomy & Biology)

  • Jian Yan

    (Inovio Pharmaceuticals)

  • Jingjing Jiang

    (Inovio Pharmaceuticals)

  • Seleeke Flingai

    (The Wistar Institute of Anatomy & Biology)

  • Amir S. Khan

    (Inovio Pharmaceuticals)

  • Kar Muthumani

    (The Wistar Institute of Anatomy & Biology)

  • Laurent Humeau

    (Inovio Pharmaceuticals)

  • Lily I. Cheng

    (MedImmune)

  • Leslie Wachter-Rosati

    (MedImmune)

  • C. Kendall Stover

    (MedImmune)

  • Niranjan Y. Sardesai

    (Inovio Pharmaceuticals)

  • David B. Weiner

    (The Wistar Institute of Anatomy & Biology)

Abstract

The impact of broad-spectrum antibiotics on antimicrobial resistance and disruption of the beneficial microbiome compels the urgent investigation of bacteria-specific approaches such as antibody-based strategies. Among these, DNA-delivered monoclonal antibodies (DMAbs), produced by muscle cells in vivo, potentially allow the prevention or treatment of bacterial infections circumventing some of the hurdles of protein IgG delivery. Here, we optimize DNA-delivered monoclonal antibodies consisting of two potent human IgG clones, including a non-natural bispecific IgG1 candidate, targeting Pseudomonas aeruginosa. The DNA-delivered monoclonal antibodies exhibit indistinguishable potency compared to bioprocessed IgG and protect against lethal pneumonia in mice. The DNA-delivered monoclonal antibodies decrease bacterial colonization of organs and exhibit enhanced adjunctive activity in combination with antibiotics. These studies support DNA-delivered monoclonal antibodies delivery as a potential strategy to augment the host immune response to prevent serious bacterial infections, and represent a significant advancement toward broader practical delivery of monoclonal antibody immunotherapeutics for additional infectious pathogens.

Suggested Citation

  • Ami Patel & Antonio DiGiandomenico & Ashley E. Keller & Trevor R. F. Smith & Daniel H. Park & Stephanie Ramos & Katherine Schultheis & Sarah T. C. Elliott & Janess Mendoza & Kate E. Broderick & Megan , 2017. "An engineered bispecific DNA-encoded IgG antibody protects against Pseudomonas aeruginosa in a pneumonia challenge model," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00576-7
    DOI: 10.1038/s41467-017-00576-7
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    Cited by:

    1. Elizabeth M. Parzych & Jianqiu Du & Ali R. Ali & Katherine Schultheis & Drew Frase & Trevor R. F. Smith & Jiayan Cui & Neethu Chokkalingam & Nicholas J. Tursi & Viviane M. Andrade & Bryce M. Warner & , 2022. "DNA-delivered antibody cocktail exhibits improved pharmacokinetics and confers prophylactic protection against SARS-CoV-2," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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