Immune correlates of postexposure vaccine protection against Marburg virus

• Published in: Scientific reports Vol. 10; no. 1; p. 3071
• Main Authors: Woolsey, Courtney, Jankeel, Allen, Matassov, Demetrius, Geisbert, Joan B., Agans, Krystle N., Borisevich, Viktoriya, Cross, Robert W., Deer, Daniel J., Fenton, Karla A., Latham, Theresa E., Gerardi, Cheryl S., Mire, Chad E., Eldridge, John H., Messaoudi, Ilhem, Geisbert, Thomas W.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.02.2020; Nature Publishing Group
• Subjects: 13/31; 38/91; 631/326/590/1867; 631/326/596/2041; Animals; Antibodies, Viral - biosynthesis; Antibodies, Viral - immunology; Antiviral drugs; Cytokines - blood; Cytotoxicity, Immunologic; Disease transmission; Dose-Response Relationship, Immunologic; Down-Regulation - genetics; Female; Filoviridae; Gene mapping; Histocompatibility antigen HLA; Humanities and Social Sciences; Immune checkpoint; Immunization; Immunoregulation; Immunostimulation; Infectious diseases; Inflammation - blood; Inflammation - immunology; Interferon; Interferons - genetics; Interferons - metabolism; Killer Cells, Natural - immunology; Lymphocytes T; Macaca mulatta - immunology; Macaca mulatta - virology; Male; Marburg disease; Marburg Virus Disease - blood; Marburg Virus Disease - genetics; Marburg Virus Disease - immunology; Marburg Virus Disease - virology; Marburgvirus - immunology; Medical prognosis; Monocytes; multidisciplinary; PD-1 protein; Peripheral blood; Post-Exposure Prophylaxis; Recombination, Genetic - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; Science; Science (multidisciplinary); Stomatitis; T-Lymphocytes, Helper-Inducer - immunology; Th1 Cells - immunology; Th2 Cells - immunology; Transcription; Transcriptome - genetics; Up-Regulation - genetics; Vaccines; Vectors; Vesiculovirus - genetics; Viral Load - immunology; Viral Vaccines - immunology; Viruses
• DOI: 10.1038/s41598-020-59976-3
• ISSN: 2045-2322

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.