An engineered bispecific DNA-encoded IgG antibody protects against Pseudomonas aeruginosa in a pneumonia challenge model
| Autor: | Antonio DiGiandomenico, Karuppiah Muthumani, Ashley E. Keller, Niranjan Y. Sardesai, Leslie Wachter-Rosati, Lily Cheng, Janess M. Mendoza, David B. Weiner, Laurent Humeau, Stephanie Ramos, C. Kendall Stover, Daniel H. Park, Jingjing Jiang, Seleeke Flingai, Amir S. Khan, Kate E. Broderick, Sarah T. C. Elliott, Jian Yan, Ami Patel, Katherine Schultheis, Megan C. Wise, Trevor R.F. Smith |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.drug_class Science Antibiotics General Physics and Astronomy Biology Monoclonal antibody medicine.disease_cause Protein Engineering General Biochemistry Genetics and Molecular Biology Immunoglobulin G Article Microbiology 03 medical and health sciences Mice Antibiotic resistance Immune system In vivo Antibodies Bispecific medicine Pneumonia Bacterial Animals Humans Pseudomonas Infections lcsh:Science Mice Inbred BALB C Multidisciplinary Pseudomonas aeruginosa Antibodies Monoclonal General Chemistry Antibodies Bacterial 030104 developmental biology HEK293 Cells Immunology biology.protein lcsh:Q Antibody |
| Zdroj: | Nature Communications Nature Communications, Vol 8, Iss 1, Pp 1-11 (2017) |
| ISSN: | 2041-1723 |
| Popis: | 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. DNA-delivered monoclonal antibodies (DMAbs) can be produced by muscle cells in vivo, potentially allowing prevention or treatment of infectious diseases. Here, the authors show that two DMAbs targeting Pseudomonas aeruginosa proteins confer protection against lethal pneumonia in mice. |
| Databáze: | OpenAIRE |
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