Neutralizing activity of anti-respiratory syncytial virus monoclonal antibody produced in Nicotiana benthamiana

Hum Vaccin Immunother. 2024 Dec 31;20(1):2327142. doi: 10.1080/21645515.2024.2327142. Epub 2024 Mar 20.

Abstract

Respiratory syncytial virus (RSV) is a highly contagious virus that affects the lungs and respiratory passages of many vulnerable people. It is a leading cause of lower respiratory tract infections and clinical complications, particularly among infants and elderly. It can develop into serious complications such as pneumonia and bronchiolitis. The development of RSV vaccine or immunoprophylaxis remains highly active and a global health priority. Currently, GSK's Arexvy™ vaccine is approved for the prevention of lower respiratory tract disease in older adults (>60 years). Palivizumab and currently nirsevimab are the approved monoclonal antibodies (mAbs) for RSV prevention in high-risk patients. Many studies are ongoing to develop additional therapeutic antibodies for preventing RSV infections among newborns and other susceptible groups. Recently, additional antibodies have been discovered and shown greater potential for development as therapeutic alternatives to palivizumab and nirsevimab. Plant expression platforms have proven successful in producing recombinant proteins, including antibodies, offering a potential cost-effective alternative to mammalian expression platforms. Hence in this study, an attempt was made to use a plant expression platform to produce two anti-RSV fusion (F) mAbs 5C4 and CR9501. The heavy-chain and light-chain sequences of both these antibodies were transiently expressed in Nicotiana benthamiana plants using a geminiviral vector and then purified using single-step protein A affinity column chromatography. Both these plant-produced mAbs showed specific binding to the RSV fusion protein and demonstrate effective viral neutralization activity in vitro. These preliminary findings suggest that plant-produced anti-RSV mAbs are able to neutralize RSV in vitro.

Keywords: Nicotiana benthamiana; RSV-fusion protein; Respiratory syncytial virus; germinivirus; immunoprophylaxis, viral infection; monoclonal antibody; recombinant expression.

MeSH terms

  • Aged
  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Humans
  • Infant
  • Infant, Newborn
  • Mammals / metabolism
  • Nicotiana / genetics
  • Palivizumab / therapeutic use
  • Respiratory Syncytial Virus Infections* / prevention & control
  • Respiratory Syncytial Virus Vaccines*
  • Respiratory Syncytial Virus, Human*
  • Viral Fusion Proteins / genetics

Substances

  • Palivizumab
  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Antibodies, Neutralizing
  • Viral Fusion Proteins
  • Respiratory Syncytial Virus Vaccines

Grants and funding

This research is funded by Thailand Science research and Innovation Fund Chulalongkorn University and the NSRF via the Program Management Unit for Human Resources & Institutional Development, Research, and Innovation [grant number B13F660137].