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 Gorantla, S.
Right arrow Articles by Poluektova, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gorantla, S.
Right arrow Articles by Poluektova, L.

 Previous Article  |  Next Article 

Journal of Virology, February 2005, p. 2124-2132, Vol. 79, No. 4
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.4.2124-2132.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Human Dendritic Cells Transduced with Herpes Simplex Virus Amplicons Encoding Human Immunodeficiency Virus Type 1 (HIV-1) gp120 Elicit Adaptive Immune Responses from Human Cells Engrafted into NOD/SCID Mice and Confer Partial Protection against HIV-1 Challenge

Santhi Gorantla,1 Kathlyn Santos,2 VaKara Meyer,1 Stephen Dewhurst,2 William J. Bowers,3,4 Howard J. Federoff,2,3,4 Howard E. Gendelman,1,5* and Larisa Poluektova1

Center for Neurovirology and Neurodegenerative Disorders and Departments of Pharmacology,1 Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, and Departments of,5 Microbiology and Immunology,2 Neurology,3 Center for Aging and Developmental Biology, Cancer Center, University of Rochester Medical Center, Rochester, New York4

Received 26 July 2004/ Accepted 30 September 2004

Small-animal models are needed to test human immunodeficiency virus (HIV) vaccine efficacy following viral challenge. To this end, we examined HIV-1-specific immune responses following immunization of nonobese diabetic-severe combined immunodeficient mice that were repopulated with human peripheral blood lymphocytes (hu-PBL-NOD/SCID mice). Autologous dendritic cells (DC) were transduced ex vivo with replication-defective, helper virus-free, herpes simplex virus type 1 (HSV-1) amplicons that expressed HIV-1 gp120 and were then injected into the hu-PBL-NOD/SCID mice. This resulted in primary HIV-1-specific humoral and cellular immune responses. Serum samples from vaccinated animals contained human immunoglobulin G that reacted with HIV-1 Env proteins by enzyme-linked immunosorbent assay and neutralized the infectivity of HIV-1 LAI and ADA strains. T cells isolated from the mice responded to viral antigens by producing gamma interferon when analyzed by enzyme-linked immunospot assay. Importantly, exposure of the vaccinated animals to infectious HIV-1 demonstrated partial protection against infectious HIV-1 challenge. This was reflected by a reduction in HIV-1ADA and by protection of the engrafted human CD4+ T lymphocytes against HIV-1LAI-induced cytotoxicity. These data demonstrate that transduction of DC by HSV amplicon vectors expressing HIV-1 gp120 induce virus-specific immune responses in hu-PBL-NOD/SCID mice. This mouse model may be a useful tool to evaluate human immune responses and protection against viral infection following vaccination.

* Corresponding author. Mailing address: Center for Neurovirology and Neurodegenerative Disorders, 985880 Nebraska Medical Center, Omaha, NE 68198-5880. Phone: (402) 559-8920. Fax: (402) 559-8922. E-mail: hegendel{at}unmc.edu.

Journal of Virology, February 2005, p. 2124-2132, Vol. 79, No. 4
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.4.2124-2132.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Brainard, D. M., Seung, E., Frahm, N., Cariappa, A., Bailey, C. C., Hart, W. K., Shin, H.-S., Brooks, S. F., Knight, H. L., Eichbaum, Q., Yang, Y.-G., Sykes, M., Walker, B. D., Freeman, G. J., Pillai, S., Westmoreland, S. V., Brander, C., Luster, A. D., Tager, A. M. (2009). Induction of Robust Cellular and Humoral Virus-Specific Adaptive Immune Responses in Human Immunodeficiency Virus-Infected Humanized BLT Mice. J. Virol. 83: 7305-7321 [Abstract] [Full Text]  
  • Dou, H., Destache, C. J., Morehead, J. R., Mosley, R. L., Boska, M. D., Kingsley, J., Gorantla, S., Poluektova, L., Nelson, J. A., Chaubal, M., Werling, J., Kipp, J., Rabinow, B. E., Gendelman, H. E. (2006). Development of a macrophage-based nanoparticle platform for antiretroviral drug delivery. Blood 108: 2827-2835 [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»