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A High Titer Anti RSV Polyclonal Antibody (RI-002) Prevents Infection with Palivizumab Resistant (PR) RSV in Cotton Rats and Achieves Greater Neutralizing RSV Activity As Compared to Palivizumab
Sunday, March 6, 2016
South Exhibit Hall H (Convention Center)
James J Mond, MD PhD, Brian Gilbert
Rationale:

To determine whether the multiple anti RSV specificities in RI-002 interact with a palivizumab resistant strain of  RSV and to evaluate the RSV neutralizing activity of RI-002 as compared to Palivizumab.

Methods:

A palivizumab resistant mutant of RSV/A Tracy was generated after serial passage in increasing concentrations of palivizumab. The resistant strain had a single amino acid substitution at position 262. Palivizumab was injected into cotton rats at 15mg/kg and RI-002 at 1500mg/kg followed one day later by intranasal inoculation with wild type or palivizumab resistant RSV. 4 days later lungs were lavaged and RSV quantified by a semi-quantitative plaque assay.

Results:

RI-002 inhibited viral replication in the lung of rats infected with wild type and resistant RSV viruses (p<0.00001) while palivizumab had comparable inhibitory effects to RI-002 on the wild type virus but no effect on the resistant strain. Furthermore the titers of neutralizing antibody in the sera of cotton rats was greater for RI-002 as compared to palivizumab (P < 0.0039)

Conclusions:

There have been many reports of patients who have failed palivizumab treatment and who have been shown to harbor palivizumab resistant strains of RSV. Whether the emergence of resistant RSV strains accounts for the limited success of this monoclonal antibody is unknown. RI-002 has recently successfully completed a phase three trial in patients with primary immune deficiency disease with a very favorable outcome of primary and secondary endpoints. Whether this reflects the unique antibody profile of this IVIG remains to be determined.