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Journal of Virology, March 2001, p. 2368-2376, Vol. 75, No. 5
Departments of
Pathology,1 Obstetrics and
Gynecology,5 Molecular Microbiology and
Immunology,3 and
Oncology,4 Johns Hopkins Medical
Institutions, Baltimore, Maryland, and Department of Obstetrics
and Gynecology, National Taiwan University Hospital, National
Taiwan University, Taipei, Taiwan2
Received 23 August 2000/Accepted 4 December 2000
Recently, self-replicating and self-limiting RNA vaccines (RNA
replicons) have emerged as an important form of nucleic acid vaccines.
Self-replicating RNA eventually causes lysis of transfected cells and
does not raise the concern associated with naked DNA vaccines of
integration into the host genome. This is particularly important for
development of vaccines targeting proteins that are potentially
oncogenic. However, the potency of RNA replicons is significantly
limited by their lack of intrinsic ability to spread in vivo. The
herpes simplex virus type 1 protein VP22 has demonstrated the
remarkable property of intercellular transport and provides the
opportunity to enhance RNA replicon vaccine potency. We therefore
created a novel fusion of VP22 with a model tumor antigen, human
papillomavirus type 16 E7, in a Sindbis virus RNA replicon vector. The
linkage of VP22 with E7 resulted in a significant enhancement of
E7-specific CD8+ T-cell activities in vaccinated mice and
converted a less effective RNA replicon vaccine into one with
significant potency against E7-expressing tumors. These results
indicate that fusion of VP22 to an antigen gene may greatly enhance the
potency of RNA replicon vaccines.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.5.2368-2376.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Enhancement of Sindbis Virus Self-Replicating RNA
Vaccine Potency by Linkage of Herpes Simplex Virus Type 1 VP22
Protein to Antigen


*
Corresponding author. Mailing address: Department of
Pathology, The Johns Hopkins University School of Medicine, Ross
Research Building, Room 659, 720 Rutland Ave., Baltimore, MD 21205. Phone: (410) 614-3899. Fax: (410) 614-3548. E-mail:
wutc{at}jhmi.edu.
Present address: Department of Pathology, School of Medicine,
Kaohsiung Medical University, Kaohsiung, Taiwan.
Present address: Department of Obstetrics and Gynecology, National
Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan.
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