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

Grant support

This work was supported by the European Union through the Sixth European Research Framework Programme (project number 2005-019043 RMV-HIV). The funding was granted to the RMV HIV consortium, including The National Institute for Biological Standards and Control (NIBSC; Potters Bar, Hertfordshire, UK), the Centre Cochin-Pasteur d'Essais Vaccinaux, Hôpital Cochin (Paris, France), Ghent University, Centre for Vaccinology (Ghent, Belgium), St. George's University of London (London, UK), GlaxoSmithKline Biologicals (Rixensart, Belgium) and the Institut Pasteur (Paris, France). Funding to attend meetings was provided by EUROPRISE Network of Excellence on HIV vaccines and Microbicides (EC FP6 grant 037611). RS, NA, NR and MP were funded in part by the NIHR Centre for Research in Health Protection at the Health Protection Agency. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.