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

Front Immunol. 2024 Jan 3:14:1279003. doi: 10.3389/fimmu.2023.1279003. eCollection 2023.

Abstract

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.

Keywords: adverse events; biomarkers; immunogenicity; innate plasma signature; rVSVΔG-ZEBOV-GP.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Viral*
  • Biomarkers
  • Democratic Republic of the Congo
  • Ebola Vaccines*
  • Europe
  • Follow-Up Studies
  • Humans
  • North America
  • Vaccination

Substances

  • Antibodies, Viral
  • Ebola Vaccines
  • Biomarkers

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 116068 (VSV-EBOPLUS project) and No 115842 (VSV-EBOVAC project). This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation program and EFPIA. Conduction of the North American trial was funded in part with Federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority, under contract number HHSO100201500002C.