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Journal of Virology, October 2000, p. 9281-9293, Vol. 74, No. 19
0022-538X/00/$04.00+0

Monoclonal Antibodies against the Adeno-Associated Virus Type 2 (AAV-2) Capsid: Epitope Mapping and Identification of Capsid Domains Involved in AAV-2-Cell Interaction and Neutralization of AAV-2 Infection

Christiane E. Wobus,1 Barbara Hügle-Dörr,2 Anne Girod,3 Gabriele Petersen,2 Michael Hallek,3 and Jürgen A. Kleinschmidt1,*

Forschungsschwerpunkt Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum,1 and Institut für Molekulare Genetik, Universität Heidelberg, Heidelberg,2 and Genzentrum München, Munich,3 Germany

Received 20 March 2000/Accepted 14 July 2000

The previously characterized monoclonal antibodies (MAbs) A1, A69, B1, and A20 are directed against assembled or nonassembled adeno-associated virus type 2 (AAV-2) capsid proteins (A. Wistuba, A. Kern, S. Weger, D. Grimm, and J. A. Kleinschmidt, J. Virol. 71:1341-1352, 1997). Here we describe the linear epitopes of A1, A69, and B1 which reside in VP1, VP2, and VP3, respectively, using gene fragment phage display library, peptide scan, and peptide competition experiments. In addition, MAbs A20, C24-B, C37-B, and D3 directed against conformational epitopes on AAV-2 capsids were characterized. Epitope sequences on the capsid surface were identified by enzyme-linked immunoabsorbent assay using AAV-2 mutants and AAV serotypes, peptide scan, and peptide competition experiments. A20 neutralizes infection following receptor attachment by binding an epitope formed during AAV-2 capsid assembly. The newly isolated antibodies C24-B and C37-B inhibit AAV-2 binding to cells, probably by recognizing a loop region involved in binding of AAV-2 to the cellular receptor. In contrast, binding of D3 to a loop near the predicted threefold spike does not neutralize AAV-2 infection. The identified antigenic regions on the AAV-2 capsid surface are discussed with respect to their possible roles in different steps of the viral life cycle.

* Corresponding author. Mailing address: Angewandte Tumorvirologie (F0100), DKFZ, Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany. Phone: 49-6221-424978. Fax: 49-6221-424962. E-mail: J.Kleinschmidt{at}DKFZ-Heidelberg.de.

Journal of Virology, October 2000, p. 9281-9293, Vol. 74, No. 19
0022-538X/00/$04.00+0


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