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Journal of Virology, September 2001, p. 7848-7853, Vol. 75, No. 17
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.17.7848-7853.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Immunization with a Pentameric L1 Fusion Protein
Protects against Papillomavirus Infection
Hang
Yuan,1
Patricia A.
Estes,2
Yan
Chen,1
Joseph
Newsome,1
Vanessa A.
Olcese,1
Robert L.
Garcea,2 and
Richard
Schlegel1,*
Department of Pathology, Georgetown
University School of Medicine, Washington, D.C.
20007,1 and Section of Pediatric
Hematology/Oncology, University of Colorado School of Medicine, Denver,
Colorado 802622
Received 22 January 2001/Accepted 23 May 2001
The prophylactic papillomavirus vaccines currently in clinical
trials are composed of viral L1 capsid protein that is synthesized in
eukaryotic expression systems and purified in the form of virus-like particles (VLPs). To evaluate whether VLPs are necessary for effective vaccination, we expressed the L1 protein as a glutathione
S-transferase (GST) fusion protein in Escherichia
coli and assayed its immunogenic activity in an established
canine oral papillomavirus (COPV) model that previously validated the
efficacy of VLP vaccines. The GST-COPV L1 fusion protein formed
pentamers, but these capsomere-like structures did not assemble into
VLPs. Despite the lack of VLP formation, the GST-COPV L1 protein
retained its native conformation as determined by reactivity with
conformation-specific anti-COPV antibodies. Most importantly, the
GST-COPV L1 pentamers completely protected dogs from high-dose viral
infection of their oral mucosa. L1 fusion proteins expressed in
bacteria represent an economical alternative to VLPs as a human
papillomavirus vaccine.
*
Corresponding author. Mailing address: Department of
Pathology, Georgetown University School of Medicine, 3900 Reservoir
Rd., Washington, DC 20007. Phone: (202) 687-1704. Fax: (202) 687-8934. E-mail: schleger{at}georgetown.edu.
Journal of Virology, September 2001, p. 7848-7853, Vol. 75, No. 17
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.17.7848-7853.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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