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

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

Author information

1
Selecta Biosciences, 480 Arsenal Street, Building One, Watertown, MA 02472, USA.
2
Selecta Biosciences, 480 Arsenal Street, Building One, Watertown, MA 02472, USA. Electronic address: kkishimoto@selectabio.com.

Abstract

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

PMID:
24583006
DOI:
10.1016/j.vaccine.2014.02.024
[Indexed for MEDLINE]
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