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This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0901373v1 183/10/6338    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Collarini, E. J. Articles by Kauvar, L. M. PubMed PubMed Citation Articles by Collarini, E. J. Articles by Kauvar, L. M.

Potent High-Affinity Antibodies for Treatment and Prophylaxis of Respiratory Syncytial Virus Derived from B Cells of Infected Patients

Ellen J. Collarini,^* F. Eun-Hyung Lee, Orit Foord,^* Minha Park,^* Gizette Sperinde,^* Hai Wu,^* William D. Harriman,^* Stephen F. Carroll,^* Stote L. Ellsworth,^* Larry J. Anderson, Ralph A. Tripp, Edward E. Walsh, Bruce A. Keyt,^* and Lawrence M. Kauvar¹

^*Trellis Bioscience, South San Francisco, CA 94080; University of Rochester Medical Center, Rochester, NY 14642; Centers for Disease Control, Atlanta, GA 30333; and University of Georgia, Athens, GA 30602

Native human Abs represent attractive drug candidates; however, the low frequency of B cells expressing high-quality Abs has posed a barrier to discovery. Using a novel single-cell phenotyping technology, we have overcome this barrier to discover human Abs targeting the conserved but poorly immunogenic central motif of respiratory syncytial virus (RSV) G protein. For the entire cohort of 24 subjects with recent RSV infection, B cells producing Abs meeting these stringent specificity criteria were rare, <10 per million. Several of the newly cloned Abs bind to the RSV G protein central conserved motif with very high affinity (K_d 1–24 pM). Two of the Abs were characterized in detail and compared with palivizumab, a humanized mAb against the RSV F protein. Relative to palivizumab, the anti-G Abs showed improved viral neutralization potency in vitro and enhanced reduction of infectious virus in a prophylaxis mouse model. Furthermore, in a mouse model for postinfection treatment, both anti-G Abs were significantly more effective than palivizumab at reducing viral load. The combination of activity in mouse models for both prophylaxis and treatment makes these high-affinity human-derived Abs promising candidates for human clinical testing.

The findings and conclusions in this report are those of the authors and do not necessarily represent the views of Centers for Disease Control and Prevention.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Address correspondence and reprint requests to Dr. Lawrence M. Kauvar, Trellis Bioscience, Inc., 2-B Corporate Drive, South San Francisco, CA 94080. E-mail address: Lkauvar{at}trellisbio.com

² Abbreviation used in this paper: RSV, respiratory syncytial virus.