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Journal of Virology, March 1999, p. 1974-1979, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Generation of Neutralizing Human Monoclonal
Antibodies against Parvovirus B19 Proteins
Andreas
Gigler,1
Simone
Dorsch,1
Andrea
Hemauer,1
Constance
Williams,2
Sonnie
Kim,3
Neal S.
Young,3
Susan
Zolla-Pazner,2,4
Hans
Wolf,1
Miroslaw K.
Gorny,2 and
Susanne
Modrow1,*
Institut für Medizinische Mikrobiologie
und Hygiene, Universität Regensburg, 93053 Regensburg,
Germany1;
Department of Pathology, New
York University Medical Center, New York, New York
100162;
Hematology Branch, National
Heart, Lung, and Blood Institute, Bethesda, Maryland
208923; and
Veterans Affairs Medical
Center, New York, New York 100104
Received 10 September 1998/Accepted 9 December 1998
Infections caused by human parvovirus B19 are known to be
controlled mainly by neutralizing antibodies. To analyze the immune reaction against parvovirus B19 proteins, four cell lines secreting human immunoglobulin G monoclonal antibodies (MAbs) were generated from
two healthy donors and one human immunodeficiency virus type 1-seropositive individual with high serum titers against parvovirus. One MAb is specific for nonstructural protein NS1 (MAb 1424), two MAbs
are specific for the unique region of minor capsid protein VP1 (MAbs
1418-1 and 1418-16), and one MAb is directed to major capsid protein
VP2 (MAb 860-55D). Two MAbs, 1418-1 and 1418-16, which were generated
from the same individual have identity in the cDNA sequences encoding
the variable domains, with the exception of four base pairs resulting
in only one amino acid change in the light chain. The NS1- and
VP1-specific MAbs interact with linear epitopes, whereas the recognized
epitope in VP2 is conformational. The MAbs specific for the structural
proteins display strong virus-neutralizing activity. The VP1- and
VP2-specific MAbs have the capacity to neutralize 50% of infectious
parvovirus B19 in vitro at 0.08 and 0.73 µg/ml, respectively,
demonstrating the importance of such antibodies in the clearance of B19
viremia. The NS1-specific MAb mediated weak neutralizing activity and
required 47.7 µg/ml for 50% neutralization. The human MAbs with
potent neutralizing activity could be used for immunotherapy of
chronically B19 virus-infected individuals and acutely infected
pregnant women. Furthermore, the knowledge gained regarding epitopes
which induce strongly neutralizing antibodies may be important for
vaccine development.
*
Corresponding author. Mailing address: Institut
für Medizinische Mikrobiologie und Hygiene, Universität
Regensburg, Franz-Josef-Strauss-Allee 11, 95053 Regensburg, Germany.
Phone: 49-941-944-6454. Fax: 49-941-944-6402. E-mail:
susanne.modrow{at}klinik.uni-regensburg.de.
Journal of Virology, March 1999, p. 1974-1979, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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