Generation of a universal CD4 memory T cell recall peptide effective in humans, mice and non-human primates

Vaccine. 2014 May 19;32(24):2896-903. doi: 10.1016/j.vaccine.2014.02.024. Epub 2014 Feb 26.


CD4T cells play a key role in humoral immunity by providing help to B cells, enabling effective antibody class switching and affinity maturation. Some vaccines may generate a poor response due to a lack of effective MHC class II epitopes, resulting in ineffective helper T cell activation and recall and consequently poor humoral immunity. It may be beneficial to provide a CD4T cell helper peptide with a vaccine particularly in the case of a poorly immunogenic antigen. Such a T cell helper peptide must be promiscuous in its ability to bind a broad range of MHC class II alleles due to broad allelic variation in the human population. We designed a chimeric MHC class II peptide (TpD) with epitopes from tetanus toxoid and diphtheria toxoid, separated by an internal cathepsin cleavage site. TpD was capable of inducing a memory recall response in peripheral blood mononuclear cells from 20/20 human donors. T cells responding to TpD showed a central memory phenotype. Immunization of mice with a synthetic nicotine nanoparticle vaccine containing TpD showed that the peptide was required for robust antibody production and resulted in a long term CD4 memory T cell recall response. As a pre-clinical model two non-human primate species, rhesus macaques and cynomolgus monkeys, were immunized with a nicotine nanoparticle vaccine and evaluated for an anti-nicotine antibody response and TpD specific memory T cells. We found that 4/4 rhesus monkeys had both sustained antibody production and TpD memory T cells for the duration of the experiment (119 days). In addition 30/30 cynomolgus monkeys dosed with nicotine vaccine nanoparticles showed dose-dependent antibody generation and T cell recall response compared to saline injected controls. In summary we have developed a potent universal memory T cell helper peptide (TpD) that is active in vitro in human PBMCs and in vivo in mice and non-human primates.

Keywords: Antibodies; Epitope; Memory T cell; Nanoparticle; Vaccine.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Diphtheria Toxoid / immunology
  • Epitopes / immunology
  • Female
  • Genes, MHC Class II
  • Humans
  • Immunologic Memory*
  • Macaca fascicularis
  • Macaca mulatta
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles
  • Nicotine / immunology
  • Peptides / immunology*
  • Tetanus Toxoid / immunology
  • Vaccines, Synthetic / immunology*


  • Diphtheria Toxoid
  • Epitopes
  • Peptides
  • Tetanus Toxoid
  • Vaccines, Synthetic
  • Nicotine