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

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 C. Wise, Jian Yan, Jingjing Jiang, Seleeke Flingai, Amir S. Khan, Kar Muthumani, Laurent Humeau, Lily I. Cheng, Leslie Wachter-Rosati, C. Kendall Stover, Niranjan Y. Sardesai and David B. Weiner ()
Additional contact information
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

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: 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.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-017-00576-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00576-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-00576-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().