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Article

Systems Vaccinology for a Live Attenuated Tularemia Vaccine Reveals Unique Transcriptional Signatures That Predict Humoral and Cellular Immune Responses

1
Hope Clinic, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Decatur, GA 30030, USA
2
Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA
3
The EMMES Corporation, Rockville, MD 20850, USA
4
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA
5
Departments of Medicine and Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA
6
Biomedical Advanced Research and Development Authority, ASPR, Department of Health and Human Services, Washington, DC 20201, USA
7
Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20892, USA
8
Institute for Immunity, Transplantation and Infection, Department of Pathology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94304, USA
9
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
*
Authors to whom correspondence should be addressed.
Vaccines 2020, 8(1), 4; https://doi.org/10.3390/vaccines8010004
Received: 2 December 2019 / Revised: 19 December 2019 / Accepted: 20 December 2019 / Published: 24 December 2019
Background: Tularemia is a potential biological weapon due to its high infectivity and ease of dissemination. This study aimed to characterize the innate and adaptive responses induced by two different lots of a live attenuated tularemia vaccine and compare them to other well-characterized viral vaccine immune responses. Methods: Microarray analyses were performed on human peripheral blood mononuclear cells (PBMCs) to determine changes in transcriptional activity that correlated with changes detected by cellular phenotyping, cytokine signaling, and serological assays. Transcriptional profiles after tularemia vaccination were compared with yellow fever [YF-17D], inactivated [TIV], and live attenuated [LAIV] influenza. Results: Tularemia vaccine lots produced strong innate immune responses by Day 2 after vaccination, with an increase in monocytes, NK cells, and cytokine signaling. T cell responses peaked at Day 14. Changes in gene expression, including upregulation of STAT1, GBP1, and IFIT2, predicted tularemia-specific antibody responses. Changes in CCL20 expression positively correlated with peak CD8+ T cell responses, but negatively correlated with peak CD4+ T cell activation. Tularemia vaccines elicited gene expression signatures similar to other replicating vaccines, inducing early upregulation of interferon-inducible genes. Conclusions: A systems vaccinology approach identified that tularemia vaccines induce a strong innate immune response early after vaccination, similar to the response seen after well-studied viral vaccines, and produce unique transcriptional signatures that are strongly correlated to the induction of T cell and antibody responses. View Full-Text
Keywords: tularemia; transcriptomics; immune signaling; comparative vaccines; live attenuated vaccines tularemia; transcriptomics; immune signaling; comparative vaccines; live attenuated vaccines
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MDPI and ACS Style

Natrajan, M.S.; Rouphael, N.; Lai, L.; Kazmin, D.; Jensen, T.L.; Weiss, D.S.; Ibegbu, C.; Sztein, M.B.; Hooper, W.F.; Hill, H.; Anderson, E.J.; Johnson, R.; Sanz, P.; Pulendran, B.; Goll, J.B.; Mulligan, M.J. Systems Vaccinology for a Live Attenuated Tularemia Vaccine Reveals Unique Transcriptional Signatures That Predict Humoral and Cellular Immune Responses. Vaccines 2020, 8, 4. https://doi.org/10.3390/vaccines8010004

AMA Style

Natrajan MS, Rouphael N, Lai L, Kazmin D, Jensen TL, Weiss DS, Ibegbu C, Sztein MB, Hooper WF, Hill H, Anderson EJ, Johnson R, Sanz P, Pulendran B, Goll JB, Mulligan MJ. Systems Vaccinology for a Live Attenuated Tularemia Vaccine Reveals Unique Transcriptional Signatures That Predict Humoral and Cellular Immune Responses. Vaccines. 2020; 8(1):4. https://doi.org/10.3390/vaccines8010004

Chicago/Turabian Style

Natrajan, Muktha S., Nadine Rouphael, Lilin Lai, Dmitri Kazmin, Travis L. Jensen, David S. Weiss, Chris Ibegbu, Marcelo B. Sztein, William F. Hooper, Heather Hill, Evan J. Anderson, Robert Johnson, Patrick Sanz, Bali Pulendran, Johannes B. Goll, and Mark J. Mulligan. 2020. "Systems Vaccinology for a Live Attenuated Tularemia Vaccine Reveals Unique Transcriptional Signatures That Predict Humoral and Cellular Immune Responses" Vaccines 8, no. 1: 4. https://doi.org/10.3390/vaccines8010004

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