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Transcriptomic and Metabolic Responses to a Live-Attenuated Francisella tularensis Vaccine
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Proteomic Analysis of Human Immune Responses to Live-Attenuated Tularemia Vaccine

1
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University Medical School, Saint Louis, MO 63104, USA
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Department of Biochemistry, Emory School of Medicine, Atlanta, GA 30322, USA
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The Emmes Company, Rockville, MD 20850, USA
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Department of Pediatrics, Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, GA, 30322, USA
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Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
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Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA
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Biomedical Advanced Research and Development Authority, U. S. Department of Health and Human Services, Washington, DC 20201, USA
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Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20892, USA
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Division of Infectious Diseases and Immunology, Department of Medicine, and New York University (NYU) Langone Vaccine Center, NYU School of Medicine, New York, NY 10016, USA
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Department of Internal Medicine, Saint Louis University Medical School, Saint Louis, MO 63104, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Vaccines 2020, 8(3), 413; https://doi.org/10.3390/vaccines8030413
Received: 18 May 2020 / Revised: 5 June 2020 / Accepted: 17 June 2020 / Published: 24 July 2020
(This article belongs to the Section Attenuated/Inactivated/Live and Vectored Vaccines)
Francisella tularensis (F. tularensis) is an intracellular pathogen that causes a potentially debilitating febrile illness known as tularemia. F. tularensis can be spread by aerosol transmission and cause fatal pneumonic tularemia. If untreated, mortality rates can be as high as 30%. To study the host responses to a live-attenuated tularemia vaccine, peripheral blood mononuclear cell (PBMC) samples were assayed from 10 subjects collected pre- and post-vaccination, using both the 2D-DIGE/MALDI-MS/MS and LC-MS/MS approaches. Protein expression related to antigen processing and presentation, inflammation (PPARγ nuclear receptor), phagocytosis, and gram-negative bacterial infection was enriched at Day 7 and/or Day 14. Protein candidates that could be used to predict human immune responses were identified by evaluating the correlation between proteome changes and humoral and cellular immune responses. Consistent with the proteomics data, parallel transcriptomics data showed that MHC class I and class II-related signals important for protein processing and antigen presentation were up-regulated, further confirming the proteomic results. These findings provide new biological insights that can be built upon in future clinical studies, using live attenuated strains as immunogens, including their potential use as surrogates of protection. View Full-Text
Keywords: proteomics; human immune response; tularemia vaccine; 2D-DIGE; LC-MS/MS; antigen processing; inflammation; phagocytosis; biomarkers proteomics; human immune response; tularemia vaccine; 2D-DIGE; LC-MS/MS; antigen processing; inflammation; phagocytosis; biomarkers
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MDPI and ACS Style

Chang, Y.-H.; Duong, D.M.; Goll, J.B.; Wood, D.C.; Jensen, T.L.; Yin, L.; Gelber, C.E.; Seyfried, N.T.; Anderson, E.; Natrajan, M.S.; Rouphael, N.; Johnson, R.A.; Sanz, P.; Mulligan, M.J.; Hoft, D.F. Proteomic Analysis of Human Immune Responses to Live-Attenuated Tularemia Vaccine. Vaccines 2020, 8, 413. https://doi.org/10.3390/vaccines8030413

AMA Style

Chang Y-H, Duong DM, Goll JB, Wood DC, Jensen TL, Yin L, Gelber CE, Seyfried NT, Anderson E, Natrajan MS, Rouphael N, Johnson RA, Sanz P, Mulligan MJ, Hoft DF. Proteomic Analysis of Human Immune Responses to Live-Attenuated Tularemia Vaccine. Vaccines. 2020; 8(3):413. https://doi.org/10.3390/vaccines8030413

Chicago/Turabian Style

Chang, Yie-Hwa, Duc M. Duong, Johannes B. Goll, David C. Wood, Travis L. Jensen, Luming Yin, Casey E. Gelber, Nicholas T. Seyfried, Evan Anderson, Muktha S. Natrajan, Nadine Rouphael, Robert A. Johnson, Patrick Sanz, Mark J. Mulligan, and Daniel F. Hoft 2020. "Proteomic Analysis of Human Immune Responses to Live-Attenuated Tularemia Vaccine" Vaccines 8, no. 3: 413. https://doi.org/10.3390/vaccines8030413

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