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Immune correlates of postexposure vaccine protection against Marburg virus
- Source :
- Scientific Reports, Scientific Reports, Vol 10, Iss 1, Pp 1-18 (2020)
- Publication Year :
- 2019
-
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.
- Subjects :
- Cytotoxicity, Immunologic
Male
LAG3
Live attenuated vaccines
lcsh:Medicine
Antibodies, Viral
0302 clinical medicine
Marburg Virus Disease
lcsh:Science
Marburg virus
Recombination, Genetic
0303 health sciences
Multidisciplinary
biology
T-Lymphocytes, Helper-Inducer
Viral Load
3. Good health
Up-Regulation
Killer Cells, Natural
Vesicular stomatitis virus
Cytokines
Female
Antibody
Post-Exposure Prophylaxis
Viral load
Dose-Response Relationship, Immunologic
Down-Regulation
Article
03 medical and health sciences
Immune system
Th2 Cells
Immunity
medicine
Animals
RNA, Messenger
030304 developmental biology
Ebola virus and Marburg virus
Inflammation
lcsh:R
Viral Vaccines
Vesiculovirus
Th1 Cells
medicine.disease
biology.organism_classification
Virology
Macaca mulatta
Immune checkpoint
Marburgvirus
biology.protein
lcsh:Q
Interferons
Transcriptome
030215 immunology
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 10
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....5f918431681c3f684b30842324b11ca9