This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tang, J.
Right arrow Articles by Flomenberg, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tang, J.
Right arrow Articles by Flomenberg, P.

 Previous Article  |  Next Article 

Journal of Virology, October 2006, p. 10010-10020, Vol. 80, No. 20
0022-538X/06/$08.00+0     doi:10.1128/JVI.00601-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Human T-Cell Responses to Vaccinia Virus Envelope Proteins

Jie Tang,1 Mariam Murtadha,1 Matthias Schnell,2 Laurence C. Eisenlohr,2 Jay Hooper,3 and Phyllis Flomenberg1,2*

Departments of Medicine,1 Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania,2 Virology Division, USAMARIID, Fort Detrick, Maryland3

Received 24 March 2006/ Accepted 18 July 2006

One approach for a safer smallpox vaccine is to utilize recombinant subunits rather than live vaccinia virus (VACV). The products of the VACV envelope genes A27L, L1R, B5R, and A33R induce protective antibodies in animal models. We propose that proteins that elicit T-cell responses, as well as neutralizing antibodies, will be important to include in a molecular vaccine. To evaluate VACV-specific memory T-cell responses, peripheral blood mononuclear cells (PBMC) from four VACV vaccinees were tested against whole VACV and the individual envelope proteins A27, B5, L1, and A33, using gamma interferon enzyme-linked immunospot and cytokine flow cytometry assays. PBMC were stimulated with autologous dendritic cells infected with VACV or electroporated with individual VACV protein mRNAs. T-cell lines from all donors, vaccinated from 1 month to over 20 years ago, recognized all four VACV envelope proteins. Both CD4+ and CD8+ T-cell responses to each protein were detected. Further analysis focused on representative proteins B5 and A27. PBMC from a recent vaccinee exhibited high frequencies of CD4+ and CD8+ T-cell precursors to both B5 (19.8 and 20%, respectively) and A27 (6.8 and 3.7%). In comparison, B5- and A27-specific T-cell frequencies ranged from 0.4 to 1.3% in a donor vaccinated 3 years ago. Multiple CD4+ and CD8+ T-cell epitopes were identified from both A27 and B5, using overlapping 15-mer peptides. These data suggest that all four VACV envelope proteins may contribute to protective immunity, not only by inducing antibody responses, but also by eliciting T-cell responses.

* Corresponding author. Mailing address: Thomas Jefferson University, 1020 Locust Street, Rm. 329, Philadelphia, PA 19107. Phone: (215) 503-2170. Fax: (215) 923-1956. E-mail: Phyllis.flomenberg{at}mail.tju.edu.

Journal of Virology, October 2006, p. 10010-10020, Vol. 80, No. 20
0022-538X/06/$08.00+0     doi:10.1128/JVI.00601-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Meseda, C. A., Mayer, A. E., Kumar, A., Garcia, A. D., Campbell, J., Listrani, P., Manischewitz, J., King, L. R., Golding, H., Merchlinsky, M., Weir, J. P. (2009). Comparative Evaluation of the Immune Responses and Protection Engendered by LC16m8 and Dryvax Smallpox Vaccines in a Mouse Model. CVI 16: 1261-1271 [Abstract] [Full Text]  
  • Jing, L., Davies, D. H., Chong, T. M., Chun, S., McClurkan, C. L., Huang, J., Story, B. T., Molina, D. M., Hirst, S., Felgner, P. L., Koelle, D. M. (2008). An Extremely Diverse CD4 Response to Vaccinia Virus in Humans Is Revealed by Proteome-Wide T-Cell Profiling. J. Virol. 82: 7120-7134 [Abstract] [Full Text]  
  • Oseroff, C., Peters, B., Pasquetto, V., Moutaftsi, M., Sidney, J., Panchanathan, V., Tscharke, D. C., Maillere, B., Grey, H., Sette, A. (2008). Dissociation between Epitope Hierarchy and Immunoprevalence in CD8 Responses to Vaccinia Virus Western Reserve. J. Immunol. 180: 7193-7202 [Abstract] [Full Text]  
  • Berhanu, A., Wilson, R. L., Kirkwood-Watts, D. L., King, D. S., Warren, T. K., Lund, S. A., Brown, L. L., Krupkin, A. K., VanderMay, E., Weimers, W., Honeychurch, K. M., Grosenbach, D. W., Jones, K. F., Hruby, D. E. (2008). Vaccination of BALB/c Mice with Escherichia coli-Expressed Vaccinia Virus Proteins A27L, B5R, and D8L Protects Mice from Lethal Vaccinia Virus Challenge. J. Virol. 82: 3517-3529 [Abstract] [Full Text]  
  • Mitra-Kaushik, S., Cruz, J., Stern, L. J., Ennis, F. A., Terajima, M. (2007). Human Cytotoxic CD4+ T Cells Recognize HLA-DR1-Restricted Epitopes on Vaccinia Virus Proteins A24R and D1R Conserved among Poxviruses. J. Immunol. 179: 1303-1312 [Abstract] [Full Text]  
  • Assarsson, E., Sidney, J., Oseroff, C., Pasquetto, V., Bui, H.-H., Frahm, N., Brander, C., Peters, B., Grey, H., Sette, A. (2007). A Quantitative Analysis of the Variables Affecting the Repertoire of T Cell Specificities Recognized after Vaccinia Virus Infection. J. Immunol. 178: 7890-7901 [Abstract] [Full Text]  
  • Jing, L., Chong, T. M., Byrd, B., McClurkan, C. L., Huang, J., Story, B. T., Dunkley, K. M., Aldaz-Carroll, L., Eisenberg, R. J., Cohen, G. H., Kwok, W. W., Sette, A., Koelle, D. M. (2007). Dominance and Diversity in the Primary Human CD4 T Cell Response to Replication-Competent Vaccinia Virus. J. Immunol. 178: 6374-6386 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»