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Updated: Aug 21, 2026
An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
Variable resistance to palivizumab in cotton rats by respiratory syncytial virus mutants
Xiaodong Zhao1, Fu-Ping Chen, A George Megaw
1Department of Pediatrics, University of Alabama at Birmingham, 1400 6th Avenue S., Birmingham, AL 35233, USA.
Background:
Palivizumab (PZ) is the only monoclonal antibody in use against a human infectious disease. PZ is given as prophylaxis against infection with respiratory syncytial virus (RSV). An RSV escape mutant, MP4, has been shown to resist PZ prophylaxis in cotton rats.
Methods:
To further define the potential of RSV to resist prophylaxis, additional PZ-resistant viruses were selected in cell culture and were tested for susceptibility to PZ in cotton rats.
Results:
Mutant MS412 had an A-->C mutation at nucleotide position 827 in the F gene, resulting in an amino acid change from Lys to Gln at position 272. Mutant F212 had an A-->T mutation at position 816, leading to an amino acid change from Asn to Ile at position 268. In vitro, F212 had impaired growth kinetics. In cell culture, F212 was partially and MS412 was completely resistant to PZ neutralization. A single prophylactic dose of 15 mg/kg PZ protected cotton rats from infection with F212 but not with MS412.
Conclusion:
Both in vitro and in vivo, individual RSV PZ escape mutants varied in their susceptibility to PZ. Mutations associated with resistance to PZ did not always result in failure of PZ prophylaxis.
Insights
Palivizumab (PZ) prophylaxis against respiratory syncytial virus (RSV) can be resisted by certain escape mutants. While some mutations confer partial resistance, others lead to complete resistance, impacting treatment effectiveness.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Palivizumab (PZ) is the sole monoclonal antibody used for prophylaxis against human infectious diseases, specifically respiratory syncytial virus (RSV).
- RSV escape mutants, such as MP4, have demonstrated resistance to PZ prophylaxis in animal models.
Purpose of the Study:
- To investigate the potential for RSV to develop resistance to PZ prophylaxis.
- To characterize additional PZ-resistant RSV variants selected in cell culture and assess their susceptibility to PZ.
Main Methods:
- Selection of PZ-resistant RSV mutants in cell culture.
- Assessment of PZ susceptibility in vitro (neutralization) and in vivo (cotton rat model).
- Genetic characterization of mutations within the F gene of resistant mutants.
Main Results:
- Two mutants, MS412 and F212, were identified with specific mutations in the F gene, leading to amino acid changes.
- F212 exhibited impaired growth kinetics in vitro, while both F212 and MS412 showed partial and complete resistance to PZ neutralization, respectively.
- A single prophylactic dose of PZ protected cotton rats against F212 but not MS412 infection.
Conclusions:
- Individual RSV PZ escape mutants exhibit variable susceptibility to PZ.
- Mutations conferring PZ resistance do not invariably lead to the failure of PZ prophylaxis.
