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 Gorelick, R. J.
Right arrow Articles by Arthur, L. O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gorelick, R. J.
Right arrow Articles by Arthur, L. O.

 Previous Article  |  Next Article 

Journal of Virology, December 2000, p. 11935-11949, Vol. 74, No. 24
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Protection of Macaca nemestrina from Disease following Pathogenic Simian Immunodeficiency Virus (SIV) Challenge: Utilization of SIV Nucleocapsid Mutant DNA Vaccines with and without an SIV Protein Boost

Robert J. Gorelick,1 Raoul E. Benveniste,2 Jeffrey D. Lifson,1 Jason L. Yovandich,1 William R. Morton,3 LaRene Kuller,3 Bernard M. Flynn,4 Bradley A. Fisher,4 Jeffrey L. Rossio,1 Michael Piatak Jr.,1 Julian W. Bess Jr.,1 Louis E. Henderson,1 and Larry O. Arthur1,*

AIDS Vaccine Program, SAIC-Frederick,1 and Basic Research Laboratory, National Cancer Institute,2 Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201; Washington Regional Primate Research Center, University of Washington, Seattle, Washington 981953; and Animal Sciences Branch, National Cancer Institute, Bethesda, Maryland 208924

Received 15 September 1999/Accepted 21 September 2000

Molecular clones were constructed that express nucleocapsid (NC) deletion mutant simian immunodeficiency viruses (SIVs) that are replication defective but capable of completing virtually all of the steps of a single viral infection cycle. These steps include production of particles that are viral RNA deficient yet contain a full complement of processed viral proteins. The mutant particles are ultrastructurally indistinguishable from wild-type virus. Similar to a live attenuated vaccine, this approach should allow immunological presentation of a full range of viral epitopes, without the safety risks of replicating virus. A total of 11 Macaca nemestrina macaques were inoculated with NC mutant SIV expressing DNA, intramuscularly (i.m.) in one study and i.m. and subcutaneously in another study. Six control animals received vector DNA lacking SIV sequences. Only modest and inconsistent humoral responses and no cellular immune responses were observed prior to challenge. Following intravenous challenge with 20 animal infectious doses of the pathogenic SIV(Mne) in a long-term study, all control animals became infected and three of four animals developed progressive SIV disease leading to death. All 11 NC mutant SIV DNA-immunized animals became infected following challenge but typically showed decreased initial peak plasma SIV RNA levels compared to those of control animals (P = 0.0007). In the long-term study, most of the immunized animals had low or undetectable postacute levels of plasma SIV RNA, and no CD4+ T-cell depletion or clinical evidence of progressive disease, over more than 2 years of observation. Although a subset of immunized and control animals were boosted with SIV(Mne) proteins, no apparent protective benefit was observed. Immunization of macaques with DNA that codes for replication-defective but structurally complete virions appears to protect from or at least delay the onset of AIDS after infection with a pathogenic immunodeficiency virus. With further optimization, this may be a promising approach for vaccine development.

* Corresponding author. Mailing address: AIDS Vaccine Program, SAIC-Frederick, Frederick Cancer Research and Development Center, Frederick, MD 21702-1201. Phone: (301) 846-1408. Fax: (301) 846-5588. E-mail: arthur{at}avpaxp1.ncifcrf.gov.

Journal of Virology, December 2000, p. 11935-11949, Vol. 74, No. 24
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Gupta, S., Leutenegger, C. M., Dean, G. A., Steckbeck, J. D., Cole, K. S., Sparger, E. E. (2007). Vaccination of Cats with Attenuated Feline Immunodeficiency Virus Proviral DNA Vaccine Expressing Gamma Interferon. J. Virol. 81: 465-473 [Abstract] [Full Text]  
  • Smith, M. Z., Dale, C. J., De Rose, R., Stratov, I., Fernandez, C. S., Brooks, A. G., Weinfurter, J., Krebs, K., Riek, C., Watkins, D. I., O'Connor, D. H., Kent, S. J. (2005). Analysis of Pigtail Macaque Major Histocompatibility Complex Class I Molecules Presenting Immunodominant Simian Immunodeficiency Virus Epitopes. J. Virol. 79: 684-695 [Abstract] [Full Text]  
  • Akahata, W., Yang, Z.-y., Nabel, G. J. (2005). Comparative Immunogenicity of Human Immunodeficiency Virus Particles and Corresponding Polypeptides in a DNA Vaccine. J. Virol. 79: 626-631 [Abstract] [Full Text]  
  • Akahata, W., Ido, E., Akiyama, H., Uesaka, H., Enose, Y., Horiuchi, R., Kuwata, T., Goto, T., Takahashi, H., Hayami, M. (2003). DNA vaccination of macaques by a full-genome simian/human immunodeficiency virus type 1 plasmid chimera that produces non-infectious virus particles. J. Gen. Virol. 84: 2237-2244 [Abstract] [Full Text]  
  • Voss, G., Manson, K., Montefiori, D., Watkins, D. I., Heeney, J., Wyand, M., Cohen, J., Bruck, C. (2002). Prevention of Disease Induced by a Partially Heterologous AIDS Virus in Rhesus Monkeys by Using an Adjuvanted Multicomponent Protein Vaccine. J. Virol. 77: 1049-1058 [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»