Profiling the targets of protective CD8(+) T cell responses to infection

Bruder, Joseph T., Chen, Ping, Ekberg, Greg, Smith, Emily C., Lazarski, Christopher A., Myers, Bennett A., Bolton, Jessica, Sedegah, Martha, Villasante, Eileen, Richie, Thomas, King, C. Richter, Aguiar, Joao C., Doolan, Denise L., and Brough, Douglas E. (2017) Profiling the targets of protective CD8(+) T cell responses to infection. Molecular Therapy: methods & clinical development, 7. pp. 20-31.

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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 Plasmodium yoelii 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.

Item ID: 51960
Item Type: Article (Research - C1)
ISSN: 2329-0501
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This is an open access article under the CC BY license.

Funders: National Institutes of Health (NIH), US Department of Defense (DOD), Naval Medical Research Centre (NMRC)
Projects and Grants: NIH grant 1R43AIO84269-01, NIH grant 1R43AI100467-01, DOD grant A043-189-0667, NMRC Military Infectious Disease Research Program work unit number 602236N.04427.B27.A0242
Date Deposited: 10 Jan 2018 07:54
FoR Codes: 42 HEALTH SCIENCES > 4206 Public health > 420605 Preventative health care @ 50%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320404 Cellular immunology @ 25%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320405 Humoural immunology and immunochemistry @ 25%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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