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02 20, 2020;10 (1): 3071.

Immune correlates of postexposure vaccine protection against Marburg virus.

Courtney Woolsey, Allen Jankeel, Demetrius Matassov, Joan B Geisbert, Krystle N Agans, Viktoriya Borisevich, Robert W Cross, Daniel J Deer, Karla A Fenton, Theresa E Latham, Cheryl S Gerardi, Chad E Mire, John H Eldridge, Ilhem Messaoudi, Thomas W Geisbert
Author Information
  1. Courtney Woolsey: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA. ORCID
  2. Allen Jankeel: Department of Molecular Biology and Biochemistry, School of Biological Sciences, University of California, Irvine, Irvine, CA, 92697, USA.
  3. Demetrius Matassov: Department of Virology and Vaccine Vectors, Profectus BioSciences Inc., Pearl River, NY, 10965, USA.
  4. Joan B Geisbert: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
  5. Krystle N Agans: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA. ORCID
  6. Viktoriya Borisevich: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
  7. Robert W Cross: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
  8. Daniel J Deer: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
  9. Karla A Fenton: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
  10. Theresa E Latham: Department of Virology and Vaccine Vectors, Profectus BioSciences Inc., Pearl River, NY, 10965, USA.
  11. Cheryl S Gerardi: Department of Virology and Vaccine Vectors, Profectus BioSciences Inc., Pearl River, NY, 10965, USA.
  12. Chad E Mire: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA. ORCID
  13. John H Eldridge: Department of Virology and Vaccine Vectors, Profectus BioSciences Inc., Pearl River, NY, 10965, USA.
  14. Ilhem Messaoudi: Department of Molecular Biology and Biochemistry, School of Biological Sciences, University of California, Irvine, Irvine, CA, 92697, USA.
  15. Thomas W Geisbert: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA. twgeisbe@utmb.edu.
PMID: 32080323 DOI: 10.1038/s41598-020-59976-3

Abstract

Postexposure immunization can prevent disease and reduce transmission following pathogen exposure. The rapid immunostimulatory properties of recombinant vesicular stomatitis virus (rVSV)-based vaccines make them suitable postexposure treatments against the filoviruses Ebola virus and Marburg virus (MARV); however, the mechanisms that drive this protection are undefined. Previously, we reported 60-75% survival of rhesus macaques treated with rVSV vectors expressing MARV glycoprotein (GP) 20-30 minutes after a low dose exposure to the most pathogenic variant of MARV, Angola. Survival in this model was linked to production of GP-specific antibodies and lower viral load. To confirm these results and potentially identify novel correlates of postexposure protection, we performed a similar experiment, but analyzed plasma cytokine levels, frequencies of immune cell subsets, and the transcriptional response to infection in peripheral blood. In surviving macaques (80-89%), we observed induction of genes mapping to antiviral and interferon-related pathways early after treatment and a higher percentage of T helper 1 (Th1) and NK cells. In contrast, the response of non-surviving macaques was characterized by hypercytokinemia; a T helper 2 signature; recruitment of low HLA-DR expressing monocytes and regulatory T-cells; and transcription of immune checkpoint (e.g., PD-1, LAG3) genes. These results suggest dysregulated immunoregulation is associated with poor prognosis, whereas early innate signaling and Th1-skewed immunity are important for survival.

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Grants

  1. U19 AI109711/NIAID NIH HHS
  2. U19 AI142785/NIAID NIH HHS
  3. UC7 AI094660/NIAID NIH HHS

MeSH Term

Animals
Antibodies, Viral
Cytokines
Cytotoxicity, Immunologic
Dose-Response Relationship, Immunologic
Down-Regulation
Female
Inflammation
Interferons
Killer Cells, Natural
Macaca mulatta
Male
Marburg Virus Disease
Marburgvirus
Post-Exposure Prophylaxis
RNA, Messenger
Recombination, Genetic
T-Lymphocytes, Helper-Inducer
Th1 Cells
Th2 Cells
Transcriptome
Up-Regulation
Vesiculovirus
Viral Load
Viral Vaccines

Chemicals

Antibodies, Viral
Cytokines
RNA, Messenger
Viral Vaccines
Interferons
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
Article has an altmetric score of 4

Word Cloud

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