Effectiveness of a novel immunogenic nanoparticle platform for Toxoplasma peptide vaccine in HLA transgenic mice

Kamal El Bissati; Ying Zhou; Debleena Dasgupta; Drew Cobb; Jitender P Dubey; Peter Burkhard; David E Lanar; Rima McLeod

doi:10.1016/j.vaccine.2014.03.092

Effectiveness of a novel immunogenic nanoparticle platform for Toxoplasma peptide vaccine in HLA transgenic mice

Vaccine. 2014 May 30;32(26):3243-8. doi: 10.1016/j.vaccine.2014.03.092. Epub 2014 Apr 13.

Authors

Kamal El Bissati¹, Ying Zhou², Debleena Dasgupta³, Drew Cobb⁴, Jitender P Dubey⁵, Peter Burkhard⁶, David E Lanar³, Rima McLeod²

Affiliations

¹ Department of Surgery, The University of Chicago, Chicago, IL 60637, USA. Electronic address: kelbissati@uchicago.edu.
² Department of Surgery, The University of Chicago, Chicago, IL 60637, USA.
³ Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910-7500, USA.
⁴ George Washington University, 2300 I St. NW Ross Hall, Room 745, Washington, DC 20037, USA.
⁵ United States Department of Agriculture, Agricultural Research Service, Beltsville Agricultural Research Center, Animal Parasitic Diseases Laboratory, Building 1001, Beltsville, MD 20705, USA.
⁶ Institute of Materials Science and Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, USA.

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.

Keywords: HLA-B7; Nanoparticles; Toxoplasma gondii; Vaccine.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD8-Positive T-Lymphocytes / immunology*
Epitopes, T-Lymphocyte / immunology
Female
HLA-B7 Antigen
Interferon-gamma / immunology
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic
Models, Molecular
Nanoparticles / administration & dosage*
Peptides / immunology
Protozoan Vaccines / immunology*
Spleen / immunology
Toxoplasma
Toxoplasmosis / prevention & control*
Vaccines, Subunit / immunology

Substances

Epitopes, T-Lymphocyte
HLA-B*07:02 antigen
HLA-B7 Antigen
Peptides
Protozoan Vaccines
Vaccines, Subunit
Interferon-gamma

Abstract

Publication types

MeSH terms

Substances

Grants and funding