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

Amitinder Kaur*, Hannah B. Sanford, Deirdre Garry, Sabine Lang, Sherry A. Klumpp, Daisuke Watanabe, Roderick T. Bronson, Jeffrey D. Lifson, Margherita Rosati, George N. Pavlakis, Barbara K. Felber, David M. Knipe, Ronald C. Desrosiers

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)199-214
Number of pages16
JournalVirology
Volume357
Issue number2
DOIs
StatePublished - Jan 20 2007

Keywords

  • AIDS vaccine
  • DNA prime
  • Recombinant HSV vectors
  • Rhesus macaque
  • SIV

ASJC Scopus subject areas

  • Virology

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