CD40L expressed from the canarypox vector, ALVAC, can boost immunogenicity of HIV-1 canarypox vaccine in mice and enhance the in vitro expansion of viral specific CD8+ T cell memory responses from HIV-1-infected and HIV-1-uninfected individuals

Vaccine. 2008 Jul 29;26(32):4062-72. doi: 10.1016/j.vaccine.2008.05.018. Epub 2008 Jun 2.

Abstract

Human immunodeficiency virus type 1 (HIV-1) canarypox vaccines are safe but poorly immunogenic. CD40 ligand (CD40L), a member of the tumor necrosis factor superfamily (TNFSF), is a pivotal costimulatory molecule for immune responses. To explore whether CD40L can be used as an adjuvant for HIV-1 canarypox vaccine, we constructed recombinant canarypox viruses expressing CD40L. Co-immunization of mice with CD40L expressing canarypox and the canarypox vaccine expressing HIV-1 proteins, vCP1452, augmented HIV-1 specific cytotoxic T lymphocyte (CTL) responses in terms of frequency, polyfunctionality and interleukin (IL)-7 receptor alpha chain (IL-7Ralpha, CD127) expression. In addition, CD40L expressed from canarypox virus could significantly augment CD4+ T cell responses against HIV-1 in mice. CD40L expressed from canarypox virus matured human monocyte-derived dendritic cells (MDDCs) in a tumor necrosis factor-alpha (TNF-alpha) independent manner, which underwent less apoptosis, and could expand ex vivo Epstein-Barr virus (EBV)-specific CTL responses from healthy human individuals and ex vivo HIV-1-specific CTL responses from HIV-1-infected individuals in the presence or absence of CD4+ T cells. Taken together, our results suggest that CD40L incorporation into poxvirus vectors could be used as a strategy to enhance their immunogenicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / chemistry
  • AIDS Vaccines / immunology
  • Adjuvants, Immunologic
  • Animals
  • Apoptosis / drug effects
  • CD40 Ligand / metabolism*
  • CD40 Ligand / pharmacology*
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology
  • Canarypox virus / immunology
  • Canarypox virus / metabolism*
  • Dendritic Cells / drug effects
  • Female
  • HIV Infections / genetics
  • HIV Infections / immunology*
  • HIV-1 / immunology
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Viral Vaccines / metabolism*

Substances

  • AIDS Vaccines
  • ALVAC vaccine
  • Adjuvants, Immunologic
  • Viral Vaccines
  • CD40 Ligand