Related Experiment Video
Updated: Mar 3, 2026
An Improved and High Throughput Respiratory Syncytial Virus RSV Micro-neutralization Assay
Published on: January 26, 2019
A highly potent extended half-life antibody as a potential RSV vaccine surrogate for all infants
Qing Zhu1, Jason S McLellan2, Nicole L Kallewaard3
1Department of Infectious Disease, MedImmune LLC, One MedImmune Way, Gaithersburg, MD 20878, USA. suzichj@medimmune.com zhuq@medimmune.com.
Insights
A new monoclonal antibody, MEDI8897, shows promise for protecting all infants from respiratory syncytial virus (RSV) with a single dose. This highly potent antibody offers a more cost-effective and practical prophylaxis than current options.
Area of Science:
- Immunology
- Virology
- Pharmacology
Background:
- Respiratory syncytial virus (RSV) poses a significant public health threat to infants.
- Current prophylaxis, palivizumab, is restricted to high-risk infants due to cost and dosing frequency.
- There is a critical need for a universally applicable RSV prevention strategy.
Purpose of the Study:
- To develop a novel monoclonal antibody for broad-spectrum RSV prophylaxis in all infants.
- To evaluate the potency, efficacy, and pharmacokinetic profile of MEDI8897 compared to palivizumab.
Main Methods:
- MEDI8897, a human antibody targeting the prefusion RSV F protein, was developed and optimized.
- Antibody binding, neutralization activity against diverse RSV strains, and in vivo efficacy in cotton rats were assessed.
- Pharmacokinetic studies in non-human primates were conducted to determine half-life.
Main Results:
- MEDI8897 demonstrated >50-fold higher neutralization activity than palivizumab against RSV A and B strains.
- In vivo, MEDI8897 was ninefold more potent in reducing viral loads in cotton rats.
- The YTE modification significantly increased MEDI8897's half-life, suggesting potential for single-dose administration.
Conclusions:
- MEDI8897 is a highly potent monoclonal antibody with a broad neutralization spectrum against RSV.
- Its enhanced potency and extended half-life support its development as a cost-effective, single-dose RSV prophylaxis for all infants.
- MEDI8897 represents a promising advancement in pediatric infectious disease prevention.
Abstract:
Prevention of respiratory syncytial virus (RSV) illness in all infants is a major public health priority. However, no vaccine is currently available to protect this vulnerable population. Palivizumab, the only approved agent for RSV prophylaxis, is limited to high-risk infants, and the cost associated with the requirement for dosing throughout the RSV season makes its use impractical for all infants. We describe the development of a monoclonal antibody as potential RSV prophylaxis for all infants with a single intramuscular dose. MEDI8897*, a highly potent human antibody, was optimized from antibody D25, which targets the prefusion conformation of the RSV fusion (F) protein. Crystallographic analysis of Fab in complex with RSV F from subtypes A and B reveals that MEDI8897* binds a highly conserved epitope. MEDI8897* neutralizes a diverse panel of RSV A and B strains with >50-fold higher activity than palivizumab. At similar serum concentrations, prophylactic administration of MEDI8897* was ninefold more potent than palivizumab at reducing pulmonary viral loads by >3 logs in cotton rats infected with either RSV A or B subtypes. MEDI8897 was generated by the introduction of triple amino acid substitutions (YTE) into the Fc domain of MEDI8897*, which led to more than threefold increased half-life in cynomolgus monkeys compared to non-YTE antibody. Considering the pharmacokinetics of palivizumab in infants, which necessitates five monthly doses for protection during an RSV season, the high potency and extended half-life of MEDI8897 support its development as a cost-effective option to protect all infants from RSV disease with once-per-RSV-season dosing in the clinic.
