ABSTRACT
We created and produced a novel self-assembling nanoparticle platform for delivery of peptide epitopes that induces CD8(+) and CD4(+)T cells that are protective against Toxoplasma gondii infection. These self-assembling polypeptide nanoparticles (SAPNs) are composed of linear peptide (LP) monomers which contain two coiled-coil oligomerization domains, the dense granule 7 (GRA720-28 LPQFATAAT) peptide and a universal CD4(+)T cell epitope (derived from PADRE). Purified LPs assemble into nanoparticles with icosahedral symmetry, similar to the capsids of small viruses. These particles were evaluated for their efficacy in eliciting IFN-γ by splenocytes of HLA-B*0702 transgenic mice and for their ability to protect against subsequent T. gondii challenge. This work demonstrates the feasibility of using this platform approach with a CD8(+) epitope that binds HLA-B7 and tests the biological activity of potentially protective peptides restricted by human major histocompatibility complex (HLA) class I molecules in HLA transgenic mice.
Subject(s)
CD8-Positive T-Lymphocytes/immunology , Nanoparticles/administration & dosage , Protozoan Vaccines/immunology , Toxoplasmosis/prevention & control , Animals , Epitopes, T-Lymphocyte/immunology , Female , HLA-B7 Antigen , Interferon-gamma/immunology , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Transgenic , Models, Molecular , Peptides/immunology , Spleen/immunology , Toxoplasma , Vaccines, Subunit/immunologyABSTRACT
Reports by the Institute of Medicine (IOM) have brought patient safety concerns to the forefront in many health care facilities. The IOM and other organizations have said that increased use of technology has the potential to increase patient safety. This article looks at the reasons behind the increase in health care errors involving patients and considers how technology could help resolve some of these problems.