Prime/boost immunization with HIV-1 MPER-V3 fusion construct enhances humoral and cellular immune responses

Immunol Lett. 2015 Dec;168(2):366-73. doi: 10.1016/j.imlet.2015.10.012. Epub 2015 Oct 27.

Abstract

Development of an effective vaccine against HIV-1 infection is a main concern in worldwide. A potent vaccine for HIV-1 requires the induction and maintenance of both humoral and cellular immunity. In this study, the levels of humoral and cellular immune responses were compared using MPER-V3 injection in three immunization strategies such as DNA/DNA, peptide/peptide, and DNA/peptide (prime-boost). MPG peptide and Montanide 720 were used as a DNA delivery system, and as a peptide adjuvant, respectively. Our results demonstrated that MPG forms stable non-covalent nanoparticles with plasmid DNA at N/P ratio of 10:1 (∼ 110-130 nm). The in vitro transfection efficiency of MPER-V3 DNA using MPG was comparable with lipofectamine and turbofect reagents as a common delivery system. In vivo prime-boost immunization using HIV-1 MPER-V3 could significantly enhance humoral and cellular immune responses as compared to control groups. The mixture of IgG1 and IgG2a was observed for each strategy, but IFN-γ production was significantly higher in prime-boost and peptide immunizations than that in DNA immunizations, inducing Th1 response. Moreover, our data showed that prime immunization with low dose of the nanoparticles (MPER-V3 DNA: MPG at ratio of 1:10) followed by MPER-V3 peptide drives T cell responses towards a Th1-type similar to high dose of the naked DNA prime/peptide boost immunization. Generally, the prime-boost strategy could improve both immune responses against MPER and especially V3 peptides suggesting its application as a promising HIV vaccine candidate in future.

Keywords: DNA vaccine; HIV; MPER-V3; MPG delivery system; Peptide vaccine; Prime-boost vaccine.

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / immunology*
  • Animals
  • DNA-Binding Proteins / administration & dosage
  • DNA-Binding Proteins / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • HEK293 Cells
  • HIV Infections / immunology*
  • HIV Infections / prevention & control
  • HIV Infections / virology
  • HIV-1 / immunology*
  • HIV-1 / physiology
  • Host-Pathogen Interactions / drug effects
  • Host-Pathogen Interactions / immunology
  • Humans
  • Immunity, Cellular / drug effects
  • Immunity, Cellular / immunology*
  • Immunity, Humoral / drug effects
  • Immunity, Humoral / immunology*
  • Immunization, Secondary / methods
  • Immunoglobulin G / immunology
  • Immunoglobulin G / metabolism
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Mice, Inbred BALB C
  • Microscopy, Atomic Force
  • Nanoparticles / administration & dosage
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Vaccination / methods

Substances

  • AIDS Vaccines
  • DNA-Binding Proteins
  • Immunoglobulin G
  • MPG peptide
  • Interferon-gamma