Proteomic Analysis of Human Immune Responses to Live-Attenuated Tularemia Vaccine
Yie-Hwa Chang,
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,
Daniel F. Hoft
Affiliations
Yie-Hwa Chang
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University Medical School, Saint Louis, MO 63104, USA
Duc M. Duong
Department of Biochemistry, Emory School of Medicine, Atlanta, GA 30322, USA
Johannes B. Goll
The Emmes Company, Rockville, MD 20850, USA
David C. Wood
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University Medical School, Saint Louis, MO 63104, USA
Travis L. Jensen
The Emmes Company, Rockville, MD 20850, USA
Luming Yin
Department of Biochemistry, Emory School of Medicine, Atlanta, GA 30322, USA
Casey E. Gelber
The Emmes Company, Rockville, MD 20850, USA
Nicholas T. Seyfried
Department of Biochemistry, Emory School of Medicine, Atlanta, GA 30322, USA
Evan Anderson
Department of Pediatrics, Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, GA, 30322, USA
Muktha S. Natrajan
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
Nadine Rouphael
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
Robert A. Johnson
Biomedical Advanced Research and Development Authority, U. S. Department of Health and Human Services, Washington, DC 20201, USA
Patrick Sanz
Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20892, USA
Mark J. Mulligan
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
Daniel F. Hoft
Department of Internal Medicine, Saint Louis University Medical School, Saint Louis, MO 63104, USA
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.
