Objective: Palivizumab(PZ) is the only monoclonal antibody presently available for use in humans against an infectious disease.RSV selected in cell culture for growth in the presence of PZ develops F gene mutations and is resistant to PZ prophylaxis in cotton rats.Here

we evaluated the potential for PZ resistant RSV to arise in vivo.Methods: Cotton rats were immunosuppressed with cyclophosphamide(CY)

administered PZ

and inoculated intranasally with RSV.Lungs were harvested 12 weeks after RSV infection

RT-PCR amplified F gene fragments were cloned into plasmids

and the nucleotide sequences of the cloned cDNAs were determined.Results: Three of the five animals had mixed populations of lung viruses

and over 50% of the clones from the 3 animals revealed F gene mutations associated with resistance to PZ.A virus completely resistant to PZ neutralization was recovered from the lung homogenate of a rat that had received PZ.Conclusion: Prolonged pulmonary replication of RSV in the presence of PZ is followed by the appearance of viruses resistant to PZ.The potential for the development of resistance is a consideration as antibody is used prophylactically against RSV and as passively administered antibody is under development for other infections

including emerging viruses and agents of biodefense.