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Title: Ability of herpes simplex virus vectors to boost immune responses to DNA vectors and to protect against challenge by simian immunodeficiency virus

Abstract

The immunogenicity and protective capacity of replication-defective herpes simplex virus (HSV) vector-based vaccines were examined in rhesus macaques. Three macaques were inoculated with recombinant HSV vectors expressing Gag, Env, and a Tat-Rev-Nef fusion protein of simian immunodeficiency virus (SIV). Three other macaques were primed with recombinant DNA vectors expressing Gag, Env, and a Pol-Tat-Nef-Vif fusion protein prior to boosting with the HSV vectors. Robust anti-Gag and anti-Env cellular responses were detected in all six macaques. Following intravenous challenge with wild-type, cloned SIV239, peak and 12-week plasma viremia levels were significantly lower in vaccinated compared to control macaques. Plasma SIV RNA in vaccinated macaques was inversely correlated with anti-Rev ELISPOT responses on the day of challenge (P value < 0.05), anti-Tat ELISPOT responses at 2 weeks post challenge (P value < 0.05) and peak neutralizing antibody titers pre-challenge (P value 0.06). These findings support continued study of recombinant herpesviruses as a vaccine approach for AIDS.

Authors:
 [1];  [2];  [2];  [2];  [2];  [3];  [4];  [5];  [6];  [6];  [7];  [3];  [2]
  1. New England Primate Research Center, Harvard Medical School, One Pine Hill Drive, P.O. Box 9102, Southborough, MA 01772-9102 (United States). E-mail: amitinder_kaur@hms.harvard.edu
  2. New England Primate Research Center, Harvard Medical School, One Pine Hill Drive, P.O. Box 9102, Southborough, MA 01772-9102 (United States)
  3. Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Ave., Boston, MA 02115-5716 (United States)
  4. Harvard Medical School, Goldenson 141, Rodent Histopathology Core, Boston, MA 02115 (United States)
  5. AIDS Vaccine Program, SAIC Frederick Inc., National Cancer Institute, Frederick, MD 21702 (United States)
  6. Human Retrovirus Section, Vaccine Branch, National Cancer Institute, Frederick, MD 21702 (United States)
  7. Human Retrovirus Pathogenesis Section, Vaccine Branch, National Cancer Institute, Frederick, MD 21702 (United States)
Publication Date:
OSTI Identifier:
20850590
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 357; Journal Issue: 2; Other Information: DOI: 10.1016/j.virol.2006.08.007; PII: S0042-6822(06)00551-4; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AIDS; ANTIBODIES; DISEASE VECTORS; HERPES SIMPLEX; PROTEINS; RECOMBINANT DNA; RNA; VACCINES; VIRUSES

Citation Formats

Kaur, Amitinder, Sanford, Hannah B., Garry, Deirdre, Lang, Sabine, Klumpp, Sherry A., Watanabe, Daisuke, Bronson, Roderick T., Lifson, Jeffrey D., Rosati, Margherita, Pavlakis, George N., Felber, Barbara K., Knipe, David M., and Desrosiers, Ronald C. Ability of herpes simplex virus vectors to boost immune responses to DNA vectors and to protect against challenge by simian immunodeficiency virus. United States: N. p., 2007. Web. doi:10.1016/j.virol.2006.08.007.
Kaur, Amitinder, Sanford, Hannah B., Garry, Deirdre, Lang, Sabine, Klumpp, Sherry A., Watanabe, Daisuke, Bronson, Roderick T., Lifson, Jeffrey D., Rosati, Margherita, Pavlakis, George N., Felber, Barbara K., Knipe, David M., & Desrosiers, Ronald C. Ability of herpes simplex virus vectors to boost immune responses to DNA vectors and to protect against challenge by simian immunodeficiency virus. United States. doi:10.1016/j.virol.2006.08.007.
Kaur, Amitinder, Sanford, Hannah B., Garry, Deirdre, Lang, Sabine, Klumpp, Sherry A., Watanabe, Daisuke, Bronson, Roderick T., Lifson, Jeffrey D., Rosati, Margherita, Pavlakis, George N., Felber, Barbara K., Knipe, David M., and Desrosiers, Ronald C. Sat . "Ability of herpes simplex virus vectors to boost immune responses to DNA vectors and to protect against challenge by simian immunodeficiency virus". United States. doi:10.1016/j.virol.2006.08.007.
@article{osti_20850590,
title = {Ability of herpes simplex virus vectors to boost immune responses to DNA vectors and to protect against challenge by simian immunodeficiency virus},
author = {Kaur, Amitinder and Sanford, Hannah B. and Garry, Deirdre and Lang, Sabine and Klumpp, Sherry A. and Watanabe, Daisuke and Bronson, Roderick T. and Lifson, Jeffrey D. and Rosati, Margherita and Pavlakis, George N. and Felber, Barbara K. and Knipe, David M. and Desrosiers, Ronald C.},
abstractNote = {The immunogenicity and protective capacity of replication-defective herpes simplex virus (HSV) vector-based vaccines were examined in rhesus macaques. Three macaques were inoculated with recombinant HSV vectors expressing Gag, Env, and a Tat-Rev-Nef fusion protein of simian immunodeficiency virus (SIV). Three other macaques were primed with recombinant DNA vectors expressing Gag, Env, and a Pol-Tat-Nef-Vif fusion protein prior to boosting with the HSV vectors. Robust anti-Gag and anti-Env cellular responses were detected in all six macaques. Following intravenous challenge with wild-type, cloned SIV239, peak and 12-week plasma viremia levels were significantly lower in vaccinated compared to control macaques. Plasma SIV RNA in vaccinated macaques was inversely correlated with anti-Rev ELISPOT responses on the day of challenge (P value < 0.05), anti-Tat ELISPOT responses at 2 weeks post challenge (P value < 0.05) and peak neutralizing antibody titers pre-challenge (P value 0.06). These findings support continued study of recombinant herpesviruses as a vaccine approach for AIDS.},
doi = {10.1016/j.virol.2006.08.007},
journal = {Virology},
number = 2,
volume = 357,
place = {United States},
year = {Sat Jan 20 00:00:00 EST 2007},
month = {Sat Jan 20 00:00:00 EST 2007}
}