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Rapid high-level production of functional HIV broadly neutralizing monoclonal antibodies in transient plant expression systems.

Publication ,  Journal Article
Rosenberg, Y; Sack, M; Montefiori, D; Forthal, D; Mao, L; Hernandez-Abanto, S; Urban, L; Landucci, G; Fischer, R; Jiang, X
Published in: PLoS One
2013

Passive immunotherapy using anti-HIV broadly neutralizing monoclonal antibodies (mAbs) has shown promise as an HIV treatment, reducing mother-to-child-transmission (MTCT) of simian/human immunodeficiency virus (SHIV) in non-human primates and decreasing viral rebound in patients who ceased receiving anti-viral drugs. In addition, a cocktail of potent mAbs may be useful as mucosal microbicides and provide an effective therapy for post-exposure prophylaxis. However, even highly neutralizing HIV mAbs used today may lose their effectiveness if resistance occurs, requiring the rapid production of new or engineered mAbs on an ongoing basis in order to counteract the viral resistance or the spread of a certain HIV-1 clade in a particular region or patient. Plant-based expression systems are fast, inexpensive and scalable and are becoming increasingly popular for the production of proteins and monoclonal antibodies. In the present study, Agrobacterium-mediated transient transfection of plants, utilizing two species of Nicotiana, have been tested to rapidly produce high levels of an HIV 89.6PΔ140env and several well-studied anti-HIV neutralizing monoclonal antibodies (b12, 2G12, 2F5, 4E10, m43, VRC01) or a single chain antibody construct (m9), for evaluation in cell-based viral inhibition assays. The protein-A purified plant-derived antibodies were intact, efficiently bound HIV envelope, and were equivalent to, or in one case better than, their counterparts produced in mammalian CHO or HEK-293 cells in both neutralization and antibody dependent viral inhibition assays. These data indicate that transient plant-based transient expression systems are very adaptable and could rapidly generate high levels of newly identified functional recombinant HIV neutralizing antibodies when required. In addition, they warrant detailed cost-benefit analysis of prolonged incubation in plants to further increase mAb production.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

3

Start / End Page

e58724

Location

United States

Related Subject Headings

  • Transfection
  • Surface Plasmon Resonance
  • Plants, Genetically Modified
  • Nicotiana
  • Humans
  • HIV Antibodies
  • General Science & Technology
  • Enzyme-Linked Immunosorbent Assay
  • Cricetinae
  • CHO Cells
 

Citation

APA
Chicago
ICMJE
MLA
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Rosenberg, Y., Sack, M., Montefiori, D., Forthal, D., Mao, L., Hernandez-Abanto, S., … Jiang, X. (2013). Rapid high-level production of functional HIV broadly neutralizing monoclonal antibodies in transient plant expression systems. PLoS One, 8(3), e58724. https://doi.org/10.1371/journal.pone.0058724
Rosenberg, Yvonne, Markus Sack, David Montefiori, Donald Forthal, Lingjun Mao, Segundo Hernandez-Abanto, Lori Urban, Gary Landucci, Rainer Fischer, and Xiaoming Jiang. “Rapid high-level production of functional HIV broadly neutralizing monoclonal antibodies in transient plant expression systems.PLoS One 8, no. 3 (2013): e58724. https://doi.org/10.1371/journal.pone.0058724.
Rosenberg Y, Sack M, Montefiori D, Forthal D, Mao L, Hernandez-Abanto S, et al. Rapid high-level production of functional HIV broadly neutralizing monoclonal antibodies in transient plant expression systems. PLoS One. 2013;8(3):e58724.
Rosenberg, Yvonne, et al. “Rapid high-level production of functional HIV broadly neutralizing monoclonal antibodies in transient plant expression systems.PLoS One, vol. 8, no. 3, 2013, p. e58724. Pubmed, doi:10.1371/journal.pone.0058724.
Rosenberg Y, Sack M, Montefiori D, Forthal D, Mao L, Hernandez-Abanto S, Urban L, Landucci G, Fischer R, Jiang X. Rapid high-level production of functional HIV broadly neutralizing monoclonal antibodies in transient plant expression systems. PLoS One. 2013;8(3):e58724.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

3

Start / End Page

e58724

Location

United States

Related Subject Headings

  • Transfection
  • Surface Plasmon Resonance
  • Plants, Genetically Modified
  • Nicotiana
  • Humans
  • HIV Antibodies
  • General Science & Technology
  • Enzyme-Linked Immunosorbent Assay
  • Cricetinae
  • CHO Cells