Refined innate plasma signature after rVSVΔG-ZEBOV-GP immunization is shared among adult cohorts in Europe and North America.

Autor:	Martinez-Murillo PA; Center of Vaccinology, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland., Huttner A; Center for Vaccinology, Geneva University Hospitals, Geneva, Switzerland.; Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland.; Faculty of Medicine, University of Geneva, Geneva, Switzerland.; Center for Clinical Research, Geneva University Hospitals, Geneva, Switzerland., Lemeille S; Center of Vaccinology, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland., Medaglini D; Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, Italy., Ottenhoff THM; Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands., Harandi AM; Department of Microbiology and Immunology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Vaccine Evaluation Centre, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada., Didierlaurent AM; Center of Vaccinology, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland., Siegrist CA; Center of Vaccinology, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.; Center for Vaccinology, Geneva University Hospitals, Geneva, Switzerland.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Jan 03; Vol. 14, pp. 1279003. Date of Electronic Publication: 2024 Jan 03 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1279003
Abstrakt:	Background: During the last decade Ebola virus has caused several outbreaks in Africa. The recombinant vesicular stomatitis virus-vectored Zaire Ebola (rVSVΔG-ZEBOV-GP) vaccine has proved safe and immunogenic but is reactogenic. We previously identified the first innate plasma signature response after vaccination in Geneva as composed of five monocyte-related biomarkers peaking at day 1 post-immunization that correlates with adverse events, biological outcomes (haematological changes and viremia) and antibody titers. In this follow-up study, we sought to identify additional biomarkers in the same Geneva cohort and validate those identified markers in a US cohort. Methods: Additional biomarkers were identified using multiplexed protein biomarker platform O-link and confirmed by Luminex. Principal component analysis (PCA) evaluated if these markers could explain a higher variability of the vaccine response (and thereby refined the initial signature). Multivariable and linear regression models evaluated the correlations of the main components with adverse events, biological outcomes, and antibody titers. External validation of the refined signature was conducted in a second cohort of US vaccinees (n=142). Results: Eleven additional biomarkers peaked at day 1 post-immunization: MCP2, MCP3, MCP4, CXCL10, OSM, CX3CL1, MCSF, CXCL11, TRAIL, RANKL and IL15. PCA analysis retained three principal components (PC) that accounted for 79% of the vaccine response variability. PC1 and PC2 were very robust and had different biomarkers that contributed to their variability. PC1 better discriminated different doses, better defined the risk of fever and myalgia, while PC2 better defined the risk of headache. We also found new biomarkers that correlated with reactogenicity, including transient arthritis (MCP-2, CXCL10, CXCL11, CX3CL1, MCSF, IL-15, OSM). Several innate biomarkers are associated with antibody levels one and six months after vaccination. Refined PC1 correlated strongly in both data sets (Geneva: r = 0.97, P < 0.001; US: r = 0.99, P< 0.001). Conclusion: Eleven additional biomarkers refined the previously found 5-biomarker Geneva signature. The refined signature better discriminated between different doses, was strongly associated with the risk of adverse events and with antibody responses and was validated in a separate cohort. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Martinez-Murillo, Huttner, Lemeille, Medaglini, Ottenhoff, Harandi, Didierlaurent and Siegrist.)
Databáze:	MEDLINE
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