Immunoprophylaxis against AIDS in macaques with a lentiviral DNA vaccine

Zhen Qian Liu, Dinesh K. Singh, Darlene Sheffer, Marilyn S. Smith, Sukhbir Dhillon, Yahia Chebloune, Ramakrishna Hegde, Shilpa Buch, Opendra Narayan

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

We earlier reported that immunization of macaques with a reverse transcriptase-deleted SHIVKU2 (ΔrtSHIVKU2) plasmid that contained HIV-1(HXB2) env and SIV gag-nef induced protection against AIDS caused by challenge virus SHIV89.6P with a heterologous env. We further deleted vif and integrase from ΔrtSHIVKU2 and substituted the 3′LTR with SV40 poly A sequences, creating Δ4SHIVKU2 (M) and a parallel construct containing gag-nef of HIV-1SF2, Δ4SHIVKU2 (H). Six macaques received two intramuscular injections of the (M) DNA, and another six received three injections of the (H) DNA. Three of the latter group received two post-challenge boosts with (M) DNA vaccine. Seven virus control macaques were inoculated with SHIV89.6P. All twelve immunized macaques were challenged with SHIV89.6P virus, and CMI responses were measured by ELISPOT assays. Virus control animals all developed progressive infection, whereas vaccinated macaques from both groups controlled virus replication, with plasma viral loads dropping to undetectable levels between weeks 6 and 126 p.i. This DNA vaccine was efficacious even though it encoded Env, Gag, and Nef that were genetically distinct from the proteins in the challenge virus. The DNA vaccine induced broad-based protection without using viral proteins to boost the immunity.

Original languageEnglish (US)
Pages (from-to)444-454
Number of pages11
JournalVirology
Volume351
Issue number2
DOIs
StatePublished - Aug 1 2006
Externally publishedYes

Keywords

  • AIDS
  • DNA Vaccines
  • Macaque
  • SHIV

ASJC Scopus subject areas

  • Virology

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