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Immunization with single-cycle SIV significantly reduces viral loads after an intravenous challenge with SIV(mac)239
Preventive and Behavioral Medicine Publications and Presentations
  • Bin Jia, Harvard Medical School
  • Sharon K Ng, Harvard Medical School
  • M. Quinn DeGottardi, Harvard Medical School
  • Michael Piatak, National Cancer Institute
  • Eloisa Yuste, Harvard Medical School
  • Angela Carville, Harvard Medical School
  • Keith G. Mansfield, Harvard Medical School
  • Wenjun Li, University of Massachusetts Medical School
  • Barbra A. Richardson, University of Washington - Seattle Campus
  • Jeffrey D. Lifson, National Cancer Institute
  • David T. Evans, Harvard Medical School
UMMS Affiliation
Department of Medicine, Division of Preventive and Behavioral Medicine
Date
1-23-2009
Document Type
Article
Subjects
Animals; Antibodies, Viral; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Immunization; Macaca mulatta; RNA, Viral; Simian Acquired Immunodeficiency Syndrome; Simian immunodeficiency virus; Vesiculovirus; Viral Load
Abstract
Strains of simian immunodeficiency virus (SIV) that are limited to a single cycle of infection were evaluated for the ability to elicit protective immunity against wild-type SIV(mac)239 infection of rhesus macaques by two different vaccine regimens. Six animals were inoculated at 8-week intervals with 6 identical doses consisting of a mixture of three different envelope variants of single-cycle SIV (scSIV). Six additional animals were primed with a mixture of cytoplasmic domain-truncated envelope variants of scSIV and boosted with two doses of vesicular stomatitis virus glycoprotein (VSV G) trans-complemented scSIV. While both regimens elicited detectable virus-specific T cell responses, SIV-specific T cell frequencies were more than 10-fold higher after boosting with VSV G trans-complemented scSIV (VSV G scSIV). Broad T cell recognition of multiple viral antigens and Gag-specific CD4(+) T cell responses were also observed after boosting with VSV G scSIV. With the exception of a single animal in the repeated immunization group, all of the animals became infected following an intravenous challenge with SIV(mac)239. However, significantly lower viral loads and higher memory CD4(+) T cell counts were observed in both immunized groups relative to an unvaccinated control group. Indeed, both scSIV immunization regimens resulted in containment of SIV(mac)239 replication after challenge that was as good as, if not better than, what has been achieved by other non-persisting vaccine vectors that have been evaluated in this challenge model. Nevertheless, the extent of protection afforded by scSIV was not as good as typically conferred by persistent infection with live, attenuated SIV. These observations have potentially important implications to the design of an effective AIDS vaccine, since they suggest that ongoing stimulation of virus-specific immune responses may be essential to achieving the degree of protection afforded by live, attenuated SIV.
Rights and Permissions
Citation: Jia B, Ng SK, DeGottardi MQ, Piatak M Jr, Yuste E, et al. (2009) Immunization with Single-Cycle SIV Significantly Reduces Viral Loads After an Intravenous Challenge with SIVmac239. PLoS Pathog 5(1): e1000272. doi:10.1371/journal.ppat.1000272 Link to article on publisher's site
Comments

Copyright 2009 Jia et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Related Resources
Link to Article in PubMed
Keywords
  • Antibodies,
  • Enzyme-linked immunoassays,
  • Immune response,
  • Memory T cells,
  • SIV,
  • T cells,
  • Viral load,
  • Viral replication
PubMed ID
19165322
Citation Information
Bin Jia, Sharon K Ng, M. Quinn DeGottardi, Michael Piatak, et al.. "Immunization with single-cycle SIV significantly reduces viral loads after an intravenous challenge with SIV(mac)239" Vol. 5 Iss. 1 (2009) ISSN: 1553-7366 (Linking)
Available at: http://works.bepress.com/wenjun_li/12/