Immunogenicity of a recombinant measles-HIV-1 clade B candidate vaccine

PLoS One. 2012;7(11):e50397. doi: 10.1371/journal.pone.0050397. Epub 2012 Nov 30.

Abstract

Live attenuated measles virus is one of the most efficient and safest vaccines available, making it an attractive candidate vector for a HIV/AIDS vaccine aimed at eliciting cell-mediated immune responses (CMI). Here we have characterized the potency of CMI responses generated in mice and non-human primates after intramuscular immunisation with a candidate recombinant measles vaccine carrying an HIV-1 insert encoding Clade B Gag, RT and Nef (MV1-F4). Eight Mauritian derived, MHC-typed cynomolgus macaques were immunised with 10(5) TCID(50) of MV1-F4, four of which were boosted 28 days later with the same vaccine. F4 and measles virus (MV)-specific cytokine producing T cell responses were detected in 6 and 7 out of 8 vaccinees, respectively. Vaccinees with either M6 or recombinant MHC haplotypes demonstrated the strongest cytokine responses to F4 peptides. Polyfunctional analysis revealed a pattern of TNFα and IL-2 responses by CD4+ T cells and TNFα and IFNγ responses by CD8+ T cells to F4 peptides. HIV-specific CD4+ and CD8+ T cells expressing cytokines waned in peripheral blood lymphocytes by day 84, but CD8+ T cell responses to F4 peptides could still be detected in lymphoid tissues more than 3 months after vaccination. Anti-F4 and anti-MV antibody responses were detected in 6 and 8 out of 8 vaccinees, respectively. Titres of anti-F4 and MV antibodies were boosted in vaccinees that received a second immunisation. MV1-F4 carrying HIV-1 Clade B inserts induces robust boostable immunity in non-human primates. These results support further exploration of the MV1-F4 vector modality in vaccination strategies that may limit HIV-1 infectivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / genetics
  • AIDS Vaccines / immunology*
  • Acquired Immunodeficiency Syndrome / immunology
  • Acquired Immunodeficiency Syndrome / prevention & control*
  • Acquired Immunodeficiency Syndrome / virology
  • Animals
  • Antibodies, Viral / biosynthesis*
  • Antibodies, Viral / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / virology
  • Gene Products, gag / genetics
  • Gene Products, gag / immunology
  • HIV-1 / immunology*
  • Humans
  • Immunity, Cellular
  • Immunization, Secondary*
  • Immunologic Memory
  • Injections, Intramuscular
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / immunology
  • Macaca fascicularis
  • Male
  • Measles Vaccine / administration & dosage
  • Measles Vaccine / genetics*
  • Measles Vaccine / immunology
  • Mice
  • RNA-Directed DNA Polymerase / genetics
  • RNA-Directed DNA Polymerase / immunology
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / immunology
  • Vaccines, Synthetic
  • nef Gene Products, Human Immunodeficiency Virus / genetics
  • nef Gene Products, Human Immunodeficiency Virus / immunology

Substances

  • AIDS Vaccines
  • Antibodies, Viral
  • Gene Products, gag
  • Interleukin-2
  • Measles Vaccine
  • Tumor Necrosis Factor-alpha
  • Vaccines, Synthetic
  • nef Gene Products, Human Immunodeficiency Virus
  • Interferon-gamma
  • RNA-Directed DNA Polymerase