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 Ulmer, J. B.
Right arrow Articles by Caulfield, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ulmer, J. B.
Right arrow Articles by Caulfield, M. J.

 Previous Article  |  Next Article 

J Virol, July 1998, p. 5648-5653, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Protective CD4+ and CD8+ T Cells against Influenza Virus Induced by Vaccination with Nucleoprotein DNA

Jeffrey B. Ulmer,dagger Tong-Ming Fu, R. Randall Deck, Arthur Friedman, Liming Guan, Corrille DeWitt, Xu Liu, Su Wang, Margaret A. Liu,dagger John J. Donnelly, and Michael J. Caulfield*

Department of Virus and Cell Biology, Merck Research Laboratories, West Point, Pennsylvania 19486

Received 14 November 1997/Accepted 2 April 1998

DNA vaccination is an effective means of eliciting both humoral and cellular immunity, including cytotoxic T lymphocytes (CTL). Using an influenza virus model, we previously demonstrated that injection of DNA encoding influenza virus nucleoprotein (NP) induced major histocompatibility complex class I-restricted CTL and cross-strain protection from lethal virus challenge in mice (J. B. Ulmer et al., Science 259:1745-1749, 1993). In the present study, we have characterized in more detail the cellular immune responses induced by NP DNA, which included robust lymphoproliferation and Th1-type cytokine secretion (high levels of gamma interferon and interleukin-2 [IL-2], with little IL-4 or IL-10) in response to antigen-specific restimulation of splenocytes in vitro. These responses were mediated by CD4+ T cells, as shown by in vitro depletion of T-cell subsets. Taken together, these results indicate that immunization with NP DNA primes both cytolytic CD8+ T cells and cytokine-secreting CD4+ T cells. Further, we demonstrate by adoptive transfer and in vivo depletion of T-cell subsets that both of these types of T cells act as effectors in protective immunity against influenza virus challenge conferred by NP DNA.

* Corresponding author. Mailing address: Merck Research Laboratories, WP 26B-111, West Point, PA 19486. Phone: (215) 652-3402. Fax: (215) 652-2142. E-mail: michael_caulfield{at}merck.com.

dagger Present address: Chiron Corporation, Emeryville, Calif.

J Virol, July 1998, p. 5648-5653, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Assarsson, E., Bui, H.-H., Sidney, J., Zhang, Q., Glenn, J., Oseroff, C., Mbawuike, I. N., Alexander, J., Newman, M. J., Grey, H., Sette, A. (2008). Immunomic Analysis of the Repertoire of T-Cell Specificities for Influenza A Virus in Humans. J. Virol. 82: 12241-12251 [Abstract] [Full Text]  
  • Carragher, D. M., Kaminski, D. A., Moquin, A., Hartson, L., Randall, T. D. (2008). A Novel Role for Non-Neutralizing Antibodies against Nucleoprotein in Facilitating Resistance to Influenza Virus. J. Immunol. 181: 4168-4176 [Abstract] [Full Text]  
  • Jeon, Y. H., Choi, Y., Yoon, S. O., Kim, C. W., Chung, J.-K. (2008). Synergistic tumoricidal effect of combined hMUC1 vaccination and hNIS radioiodine gene therapy. Molecular Cancer Therapeutics 7: 2252-2260 [Abstract] [Full Text]  
  • D'Souza, S., Romano, M., Korf, J., Wang, X.-M., Adnet, P.-Y., Huygen, K. (2006). Partial Reconstitution of the CD4+-T-Cell Compartment in CD4 Gene Knockout Mice Restores Responses to Tuberculosis DNA Vaccines.. Infect. Immun. 74: 2751-2759 [Abstract] [Full Text]  
  • Applequist, S. E., Rollman, E., Wareing, M. D., Liden, M., Rozell, B., Hinkula, J., Ljunggren, H.-G. (2005). Activation of Innate Immunity, Inflammation, and Potentiation of DNA Vaccination through Mammalian Expression of the TLR5 Agonist Flagellin. J. Immunol. 175: 3882-3891 [Abstract] [Full Text]  
  • Wang, R., Richie, T. L., Baraceros, M. F., Rahardjo, N., Gay, T., Banania, J.-G., Charoenvit, Y., Epstein, J. E., Luke, T., Freilich, D. A., Norman, J., Hoffman, S. L. (2005). Boosting of DNA Vaccine-Elicited Gamma Interferon Responses in Humans by Exposure to Malaria Parasites. Infect. Immun. 73: 2863-2872 [Abstract] [Full Text]  
  • Charo, J., Lindencrona, J. A., Carlson, L.-M., Hinkula, J., Kiessling, R. (2004). Protective Efficacy of a DNA Influenza Virus Vaccine Is Markedly Increased by the Coadministration of a Schiff Base-Forming Drug. J. Virol. 78: 11321-11326 [Abstract] [Full Text]  
  • Osorio, Y., Cohen, J., Ghiasi, H. (2004). Improved Protection from Primary Ocular HSV-1 Infection and Establishment of Latency Using Multigenic DNA Vaccines. IOVS 45: 506-514 [Abstract] [Full Text]  
  • Lobell, A., Weissert, R., Eltayeb, S., de Graaf, K. L., Wefer, J., Storch, M. K., Lassmann, H., Wigzell, H., Olsson, T. (2003). Suppressive DNA Vaccination in Myelin Oligodendrocyte Glycoprotein Peptide-Induced Experimental Autoimmune Encephalomyelitis Involves a T1-Biased Immune Response. J. Immunol. 170: 1806-1813 [Abstract] [Full Text]  
  • Heinen, P. P., Rijsewijk, F. A., de Boer-Luijtze, E. A., Bianchi, A. T. J. (2002). Vaccination of pigs with a DNA construct expressing an influenza virus M2-nucleoprotein fusion protein exacerbates disease after challenge with influenza A virus. J. Gen. Virol. 83: 1851-1859 [Abstract] [Full Text]  
  • Wolkers, M. C., Toebes, M., Okabe, M., Haanen, J. B. A. G., Schumacher, T. N. M. (2002). Optimizing the Efficacy of Epitope-Directed DNA Vaccination. J. Immunol. 168: 4998-5004 [Abstract] [Full Text]  
  • Heinen, P. P., de Boer-Luijtze, E. A., Bianchi, A. T. J. (2001). Respiratory and systemic humoral and cellular immune responses of pigs to a heterosubtypic influenza A virus infection. J. Gen. Virol. 82: 2697-2707 [Abstract] [Full Text]  
  • Tso, C.-L., Zisman, A., Pantuck, A., Calilliw, R., Hernandez, J. M., Paik, S., Nguyen, D., Gitlitz, B., Shintaku, P. I., de Kernion, J., Figlin, R., Belldegrun, A. (2001). Induction of G250-targeted and T-Cell-mediated Antitumor Activity against Renal Cell Carcinoma Using a Chimeric Fusion Protein Consisting of G250 and Granulocyte/Monocyte-Colony Stimulating Factor. Cancer Res. 61: 7925-7933 [Abstract] [Full Text]  
  • Okuda, K., Xin, K.-Q., Haruki, A., Kawamoto, S., Kojima, Y., Hirahara, F., Okada, H., Klinman, D., Hamajima, K. (2001). Transplacental Genetic Immunization After Intravenous Delivery of Plasmid DNA to Pregnant Mice. J. Immunol. 167: 5478-5484 [Abstract] [Full Text]  
  • Vignuzzi, M., Gerbaud, S., van der Werf, S., Escriou, N. (2001). Naked RNA immunization with replicons derived from poliovirus and Semliki Forest virus genomes for the generation of a cytotoxic T cell response against the influenza A virus nucleoprotein. J. Gen. Virol. 82: 1737-1747 [Abstract] [Full Text]  
  • Ahlers, J. D., Belyakov, I. M., Matsui, S., Berzofsky, J. A. (2001). Mechanisms of cytokine synergy essential for vaccine protection against viral challenge. Int Immunol 13: 897-908 [Abstract] [Full Text]  
  • Tumpey, T. M., Renshaw, M., Clements, J. D., Katz, J. M. (2001). Mucosal Delivery of Inactivated Influenza Vaccine Induces B-Cell-Dependent Heterosubtypic Cross-Protection against Lethal Influenza A H5N1 Virus Infection. J. Virol. 75: 5141-5150 [Abstract] [Full Text]  
  • Kumar, V., Maglione, J., Thatte, J., Pederson, B., Sercarz, E., Ward, E. S. (2001). Induction of a type 1 regulatory CD4 T cell response following V{beta}8.2 DNA vaccination results in immune deviation and protection from experimental autoimmune encephalomyelitis. Int Immunol 13: 835-841 [Abstract] [Full Text]  
  • O’Neill, E., Krauss, S. L., Riberdy, J. M., Webster, R. G., Woodland, D. L. (2000). Heterologous protection against lethal A/HongKong/156/97 (H5N1) influenza virus infection in C57BL/6 mice. J. Gen. Virol. 81: 2689-2696 [Abstract] [Full Text]  
  • Epstein, S. L., Stack, A., Misplon, J. A., Lo, C.-Y., Mostowski, H., Bennink, J., Subbarao, K. (2000). Vaccination with DNA encoding internal proteins of influenza virus does not require CD8+ cytotoxic T lymphocytes: either CD4+ or CD8+ T cells can promote survival and recovery after challenge. Int Immunol 12: 91-101 [Abstract] [Full Text]  
  • Rodrigues, M. M., Ribeirao, M., Pereira-Chioccola, V., Renia, L., Costa, F. (1999). Predominance of CD4 Th1 and CD8 Tc1 Cells Revealed by Characterization of the Cellular Immune Response Generated by Immunization with a DNA Vaccine Containing a Trypanosoma cruzi Gene. Infect. Immun. 67: 3855-3863 [Abstract] [Full Text]  
  • Abuodeh, R. O., Shubitz, L. F., Siegel, E., Snyder, S., Peng, T., Orsborn, K. I., Brummer, E., Stevens, D. A., Galgiani, J. N. (1999). Resistance to Coccidioides immitis in Mice after Immunization with Recombinant Protein or a DNA Vaccine of a Proline-Rich Antigen. Infect. Immun. 67: 2935-2940 [Abstract] [Full Text]  
  • Fu, T.-M., Guan, L., Friedman, A., Schofield, T. L., Ulmer, J. B., Liu, M. A., Donnelly, J. J. (1999). Dose Dependence of CTL Precursor Frequency Induced by a DNA Vaccine and Correlation with Protective Immunity Against Influenza Virus Challenge. J. Immunol. 162: 4163-4170 [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»