Enhanced control of pathogenic Simian immunodeficiency virus SIVmac239 replication in macaques immunized with an interleukin-12 plasmid and a DNA prime-viral vector boost vaccine regimen. Academic Article uri icon

Overview

MeSH

  • Adenoviridae
  • Adjuvants, Immunologic
  • Animals
  • Genetic Vectors
  • Lymph Nodes
  • Macaca mulatta
  • RNA, Viral
  • Vaccines, Synthetic
  • Viral Load
  • Viremia

MeSH Major

  • Immunization, Secondary
  • Interleukin-12
  • SAIDS Vaccines
  • Simian Acquired Immunodeficiency Syndrome
  • Simian Immunodeficiency Virus
  • Vaccination
  • Vaccines, DNA

abstract

  • DNA priming has previously been shown to elicit augmented immune responses when administered by electroporation (EP) or codelivered with a plasmid encoding interleukin-12 (pIL-12). We hypothesized that the efficacy of a DNA prime and recombinant adenovirus 5 boost vaccination regimen (DNA/rAd5) would be improved when incorporating these vaccination strategies into the DNA priming phase, as determined by pathogenic simian immunodeficiency virus SIVmac239 challenge outcome. The whole SIVmac239 proteome was delivered in 5 separate DNA plasmids (pDNA-SIV) by EP with or without pIL-12, followed by boosting 4 months later with corresponding rAd5-SIV vaccine vectors. Remarkably, after repeated low-dose SIVmac239 mucosal challenge, we demonstrate 2.6 and 4.4 log reductions of the median SIV peak and set point viral loads in rhesus macaques (RMs) that received pDNA-SIV by EP with pIL-12 compared to the median peak and set point viral loads in mock-immunized controls (P < 0.01). In 5 out of 6 infected RMs, strong suppression of viremia was observed, with intermittent "blips" in virus replication. In 2 RMs, we could not detect the presence of SIV RNA in tissue and lymph nodes, even after 13 viral challenges. RMs immunized without pIL-12 demonstrated a typical maximum of 1.5 log reduction in virus load. There was no significant difference in the overall magnitude of SIV-specific antibodies or CD8 T-cell responses between groups; however, pDNA delivery by EP with pIL-12 induced a greater magnitude of SIV-specific CD4 T cells that produced multiple cytokines. This vaccine strategy is relevant for existing vaccine candidates entering clinical evaluation, and this model may provide insights into control of retrovirus replication.

publication date

  • September 2011

has subject area

  • Adenoviridae
  • Adjuvants, Immunologic
  • Animals
  • Genetic Vectors
  • Immunization, Secondary
  • Interleukin-12
  • Lymph Nodes
  • Macaca mulatta
  • RNA, Viral
  • SAIDS Vaccines
  • Simian Acquired Immunodeficiency Syndrome
  • Simian Immunodeficiency Virus
  • Vaccination
  • Vaccines, DNA
  • Vaccines, Synthetic
  • Viral Load
  • Viremia

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3165762

Digital Object Identifier (DOI)

  • 10.1128/JVI.05060-11

PubMed ID

  • 21734035

Additional Document Info

start page

  • 9578

end page

  • 9587

volume

  • 85

number

  • 18