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Journal of Virology, March 2001, p. 2368-2376, Vol. 75, No. 5
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

Wen-Fang Cheng,1,2 Chien-Fu Hung,1 Chee-Yin Chai,1,dagger Keng-Fu Hsu,1,Dagger Liangmai He,1 Morris Ling,1 and T.-C. Wu1,3,4,5,*

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.


* 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.

dagger Present address: Department of Pathology, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Dagger Present address: Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan.


Journal of Virology, March 2001, p. 2368-2376, Vol. 75, No. 5
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.5.2368-2376.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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