The Journal of Experimental Medicine
StemCell Technologies
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 24 April 2006 doi:10.1084/jem.20052433
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 5, 1249-1258
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wille-Reece, U.
Right arrow Articles by Seder, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wille-Reece, U.
Right arrow Articles by Seder, R. A.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*D-MANNITOL
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

ARTICLE

 Toll-like receptor agonists influence the magnitude and quality of memory T cell responses after prime-boost immunization in nonhuman primates

Ulrike Wille-Reece1, Barbara J. Flynn1, Karin Loré2, Richard A. Koup2, Aaron P. Miles4, Allan Saul4, Ross M. Kedl5, Joseph J. Mattapallil3, Walter R. Weiss6, Mario Roederer3, and Robert A. Seder1

1 Cellular Immunology Section, 2 Immunology Laboratory, and 3 ImmunoTechnology Section, Vaccine Research Center, National Institutes of Health (NIH), Bethesda, MD 20892
4 Malaria Vaccine Development Branch, NIH, Rockville, MD 20852
5 3M Pharmaceuticals, St. Paul, Minnesota, MN 55144
6 Malaria Program, Naval Medical Research Center, Silver Spring, MD 20910

CORRESPONDENCE Robert A. Seder: rseder{at}mail.nih.gov

There is a remarkable heterogeneity in the functional profile (quality) of T cell responses. Importantly, the magnitude and/or quality of a response required for protection may be different depending on the infection. Here, we assessed the capacity of different Toll like receptor (TLR)-binding compounds to influence T helper cell (Th)1 and CD8+ T cell responses when used as adjuvants in nonhuman primates (NHP) with HIV Gag as a model antigen. NHP were immunized with HIV Gag protein emulsified in Montanide ISA 51, an oil-based adjuvant, with or without a TLR7/8 agonist, a TLR8 agonist, or the TLR9 ligand cytosine phosphate guanosine oligodeoxynucleotides (CpG ODN), and boosted 12 wk later with a replication-defective adenovirus-expressing HIV-Gag (rAD-Gag). Animals vaccinated with HIV Gag protein/Montanide and CpG ODN or the TLR7/8 agonist had higher frequencies of Th1 responses after primary immunization compared to all other vaccine groups. Although the rAD-Gag boost did not elevate the frequency of Th1 memory cytokine responses, there was a striking increase in HIV Gag-specific CD8+ T cell responses after the boost in all animals that had received a primary immunization with any of the TLR adjuvants. Importantly, the presence and type of TLR adjuvant used during primary immunization conferred stability and dramatically influenced the magnitude and quality of the Th1 and CD8+ T cell responses after the rAD-Gag boost. These data provide insights for designing prime-boost immunization regimens to optimize Th1 and CD8+ T cell responses.

Abbreviations used: cDC, conventional DC; CpG ODN, cytosine phosphate guanosine oligodeoxynucleotides; NHP, nonhuman primates; pDC, plasmacytoid DC; rAD, replication-defective adenovirus; TLR, Toll-like receptor.

R.M. Kedl's present address is Integrated Department of Immunology, University of Colorado Health Center, Denver, CO 80206.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS