Profiling the Targets of Protective CD8 T Cell Responses to Infection.

作者信息

Bruder Joseph T, Chen Ping, Ekberg Greg, Smith Emily C, Lazarski Christopher A, Myers Bennett A, Bolton Jessica, Sedegah Martha, Villasante Eileen, Richie Thomas L, King C Richter, Aguiar Joao C, Doolan Denise L, Brough Douglas E

机构信息

GenVec, Inc., 910 Clopper Road, Suite 220N, Gaithersburg, MD 20878, USA.

Malaria Department, Naval Medical Research Center (NMRC), 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.

出版信息

Mol Ther Methods Clin Dev. 2017 Aug 18;7:20-31. doi: 10.1016/j.omtm.2017.08.003. eCollection 2017 Dec 15.

Abstract

T cells are critical effectors of host immunity that target intracellular pathogens, such as the causative agents of HIV, tuberculosis, and malaria. The development of vaccines that induce effective cell-mediated immunity against such pathogens has proved challenging; for tuberculosis and malaria, many of the antigens targeted by protective T cells are not known. Here, we report a novel approach for screening large numbers of antigens as potential targets of T cells. Malaria provides an excellent model to test this antigen discovery platform because T cells are critical mediators of protection following immunization with live sporozoite vaccines and the specific antigen targets are unknown. We generated an adenovirus array by cloning 312 highly expressed pre-erythrocytic antigens into adenovirus vectors using high-throughput methodologies. The array was screened to identify antigen-specific CD8 T cells induced by a live sporozoite vaccine regimen known to provide high levels of sterile protection mediated by CD8 T cells. We identified 69 antigens that were targeted by CD8 T cells induced by this vaccine regimen. The antigen that recalled the highest frequency of CD8 T cells, PY02605, induced protective responses in mice, demonstrating proof of principle for this approach in identifying antigens for vaccine development.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b782/5602877/83691824e588/gr1.jpg

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