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
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
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 Morello, C. S.
Right arrow Articles by Spector, D. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Morello, C. S.
Right arrow Articles by Spector, D. H.

 Previous Article  |  Next Article 

Journal of Virology, May 2002, p. 4822-4835, Vol. 76, No. 10
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.10.4822-4835.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Development of a Vaccine against Murine Cytomegalovirus (MCMV), Consisting of Plasmid DNA and Formalin-Inactivated MCMV, That Provides Long-Term, Complete Protection against Viral Replication

Christopher S. Morello, Ming Ye, and Deborah H. Spector*

Molecular Biology Section, Division of Biology, University of California, San Diego, La Jolla, California 92093-0366

Received 4 December 2001/ Accepted 5 February 2002

We previously demonstrated that immunization of mice with plasmid DNAs (pDNAs) expressing the murine cytomegalovirus (MCMV) genes IE1-pp89 and M84 provided synergistic protection against sublethal viral challenge, while immunization with plasmids expressing putative virion proteins provided no or inconsistent protection. In this report, we sought to augment protection by increasing the breadth of the immune response. We identified another MCMV gene (m04 encoding gp34) that provided strong and consistent protection against viral replication in the spleen. We also found that immunization with a DNA pool containing 10 MCMV genes that individually were nonprotective elicited reproducible protection against low to intermediate doses of challenge virus. Moreover, inclusion of these plasmids into a mixture with gp34, pp89, and M84 DNAs provided even greater protection than did coimmunization with pp89 and M84. The highest level of protection was achieved by immunization of mice with the pool of 13 pDNAs, followed by formalin-inactivated MCMV (FI-MCMV). Immunization with FI-MCMV elicited neutralizing antibodies against salivary gland-derived MCMV, and of greatest importance, mice immunized with both the combined pDNA pool and FI-MCMV had undetectable levels of virus in the spleen and salivary glands after challenge. Intracellular cytokine staining of splenocytes from pDNA- and FI-MCMV-immunized mice showed that pDNA immunization elicited high levels of pp89- and M83-specific CD8+ T cells, whereas both pDNA and FI-MCMV immunizations generated strong CD8+-T-cell responses against virion-associated antigens. Taken together, these results show that immunization with pDNA and inactivated virus provides strong antibody and cell-mediated immunity against CMV infection.

* Corresponding author. Mailing address: MC 0366, Pacific Hall, Rm. 1220, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0366. Phone: (858) 534-9737. Fax: (858) 534-6083. E-mail: dspector{at}ucsd.edu.

Journal of Virology, May 2002, p. 4822-4835, Vol. 76, No. 10
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.10.4822-4835.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Holtappels, R., Simon, C. O., Munks, M. W., Thomas, D., Deegen, P., Kuhnapfel, B., Daubner, T., Emde, S. F., Podlech, J., Grzimek, N. K. A., Oehrlein-Karpi, S. A., Hill, A. B., Reddehase, M. J. (2008). Subdominant CD8 T-Cell Epitopes Account for Protection against Cytomegalovirus Independent of Immunodomination. J. Virol. 82: 5781-5796 [Abstract] [Full Text]  
  • Cicin-Sain, L., Bubic, I., Schnee, M., Ruzsics, Z., Mohr, C., Jonjic, S., Koszinowski, U. H. (2007). Targeted Deletion of Regions Rich in Immune-Evasive Genes from the Cytomegalovirus Genome as a Novel Vaccine Strategy. J. Virol. 81: 13825-13834 [Abstract] [Full Text]  
  • Morello, C. S., Kelley, L. A., Munks, M. W., Hill, A. B., Spector, D. H. (2007). DNA Immunization Using Highly Conserved Murine Cytomegalovirus Genes Encoding Homologs of Human Cytomegalovirus UL54 (DNA Polymerase) and UL105 (Helicase) Elicits Strong CD8 T-Cell Responses and Is Protective against Systemic Challenge. J. Virol. 81: 7766-7775 [Abstract] [Full Text]  
  • Yue, Y., Kaur, A., Eberhardt, M. K., Kassis, N., Zhou, S. S., Tarantal, A. F., Barry, P. A. (2007). Immunogenicity and Protective Efficacy of DNA Vaccines Expressing Rhesus Cytomegalovirus Glycoprotein B, Phosphoprotein 65-2, and Viral Interleukin-10 in Rhesus Macaques. J. Virol. 81: 1095-1109 [Abstract] [Full Text]  
  • Munks, M. W., Gold, M. C., Zajac, A. L., Doom, C. M., Morello, C. S., Spector, D. H., Hill, A. B. (2006). Genome-Wide Analysis Reveals a Highly Diverse CD8 T Cell Response to Murine Cytomegalovirus. J. Immunol. 176: 3760-3766 [Abstract] [Full Text]  
  • Roback, J. D. (2006). Vaccine-Enhanced Donor Lymphocyte Infusion (veDLI). ASH Education Book 2006: 486-491 [Abstract] [Full Text]  
  • Morello, C. S., Ye, M., Hung, S., Kelley, L. A., Spector, D. H. (2005). Systemic Priming-Boosting Immunization with a Trivalent Plasmid DNA and Inactivated Murine Cytomegalovirus (MCMV) Vaccine Provides Long-Term Protection against Viral Replication following Systemic or Mucosal MCMV Challenge. J. Virol. 79: 159-175 [Abstract] [Full Text]  
  • Ye, M., Morello, C. S., Spector, D. H. (2004). Multiple Epitopes in the Murine Cytomegalovirus Early Gene Product M84 Are Efficiently Presented in Infected Primary Macrophages and Contribute to Strong CD8+-T-Lymphocyte Responses and Protection following DNA Immunization. J. Virol. 78: 11233-11245 [Abstract] [Full Text]  
  • Cicin-Sain, L., Brune, W., Bubic, I., Jonjic, S., Koszinowski, U. H. (2003). Vaccination of Mice with Bacteria Carrying a Cloned Herpesvirus Genome Reconstituted In Vivo. J. Virol. 77: 8249-8255 [Abstract] [Full Text]  
  • Gallez-Hawkins, G., Villacres, M. C., Li, X., Sanborn, M. C., Lomeli, N. A., Zaia, J. A. (2003). Use of Transgenic HLA A*0201/Kb and HHD II Mice To Evaluate Frequency of Cytomegalovirus IE1-Derived Peptide Usage in Eliciting Human CD8 Cytokine Response. J. Virol. 77: 4457-4462 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»