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PreprintCC BY-NDmedRxiv

Longitudinal Filovirus Seroreactivity Following Ad26.ZEBOV (Zabdeno) and MVA-BN-Filo (Mvabea) Vaccination in the Democratic Republic of the Congo

8 more authors
  1. 1UCLA

Abstract

BackgroundFiloviruses, specifically Ebola virus (EBOV), Bundibugyo virus (BDBV), and Marburg virus (MARV), have been the etiologic agents of multiple outbreaks of severe disease in the Democratic Republic of the Congo (DRC). Two EBOV-specific vaccine regimens have been approved for use in outbreak scenarios, including the Ad26.ZEBOV/MVA-BN-Filo (Zabdeno/Mvabea) two-dose vaccine, where the MVA-BN-Filo booster dose contains EBOV, MARV, and Sudan (SUDV) virus glycoproteins (GPs) and the nucleoprotein from Tai Forest virus. While long-term immunogenicity of up to two years has been found in clinical trial settings, limited real-world data exists.

MethodsUsing a multiplexed immunoassay, samples (n=698 at baseline) collected in Mbandaka, Equateur province, DRC, between September 2023 and October 2024 were assessed for seroreactivity to six filovirus antigens (1 BDBV, 2 EBOV, 2 MARV, and 1 SUDV) at three distinct periods: baseline/pre-vaccination, 6-8 weeks post-first dose (Zabdeno), at booster administration (Mvabea), and one-year post-boost dose.

ResultsSubstantial filovirus seroreactivity was found at baseline, with 48.7% (n=340/698) of individuals being seroreactive to at least one virus antigen. High baseline seroreactivity was found against BDBV GP (31.1%, n=217/698), with lower baseline seroreactivity to EBOV GP (15.5%, n=106/698), comparatively. Overall EBOV GP seroreactivity increased to 66.8% (n=376/563) at one year-post vaccine boost and 57.6% (n=250/434) of participants were seroreactive. Despite the booster dose inclusion of SUDV GP and MARV GP, there were no substantial increases in reactivity against either antigen at subsequent timepoints. Overall filovirus seroreactivity increased at all timepoints for the entire cohort, although filovirus reactivity decreased over the study period for those who were seroreactive at baseline.

FindingsThese data highlight detection of significantly elevated seoreactivity to EBOV GP following first-dose administration of Ad26.ZEBOV, which remained relatively stable one-year post-booster dose administration. Additionally, this study identifies high levels of baseline seroreactivity to BDBV GP despite no previous documented outbreaks in this region of DRC. These data suggest that vaccination with the Ad26.ZEBOV-MVA-BN-Filo vaccine induces stable seroreactivity against EBOV GP, but not to other filovirus antigens.

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BibTeX
@misc{wallace2026longitudinal,
  title = {{Longitudinal Filovirus Seroreactivity Following Ad26.ZEBOV (Zabdeno) and MVA-BN-Filo (Mvabea) Vaccination in the Democratic Republic of the Congo}},
  author = {H. L. Wallace and M. L. Halbrook and J. P. Kompany and N. A. Hoff and S. Merritt and P. Mukadi and M. Beya and H. Kalengi and M. Tambu and Z. Mossoko and J. D. Kelly and A. H. Ball and A. To and T. Wong and H. Kavunga-Membo and L. E. Hensley and A. T. Lehrer and J. Kindrachuk and P. Mbala-Kingebeni and A. W. Rimoin},
  howpublished = {medRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.15.26365698},
  url = {https://www.medrxiv.org/content/10.64898/2026.10.15.26365698v1},
  note = {CC BY-ND},
}
RIS
TY  - UNPB
TI  - Longitudinal Filovirus Seroreactivity Following Ad26.ZEBOV (Zabdeno) and MVA-BN-Filo (Mvabea) Vaccination in the Democratic Republic of the Congo
AU  - H. L. Wallace
AU  - M. L. Halbrook
AU  - J. P. Kompany
AU  - N. A. Hoff
AU  - S. Merritt
AU  - P. Mukadi
AU  - M. Beya
AU  - H. Kalengi
AU  - M. Tambu
AU  - Z. Mossoko
AU  - J. D. Kelly
AU  - A. H. Ball
AU  - A. To
AU  - T. Wong
AU  - H. Kavunga-Membo
AU  - L. E. Hensley
AU  - A. T. Lehrer
AU  - J. Kindrachuk
AU  - P. Mbala-Kingebeni
AU  - A. W. Rimoin
PY  - 2026
DA  - 2026/10/15
PB  - medRxiv
DO  - 10.64898/2026.10.15.26365698
UR  - https://www.medrxiv.org/content/10.64898/2026.10.15.26365698v1
AB  - BackgroundFiloviruses, specifically Ebola virus (EBOV), Bundibugyo virus (BDBV), and Marburg virus (MARV), have been the etiologic agents of multiple outbreaks of severe disease in the Democratic Republic of the Congo (DRC). Two EBOV-specific vaccine regimens have been approved for use in outbreak scenarios, including the Ad26.ZEBOV/MVA-BN-Filo (Zabdeno/Mvabea) two-dose vaccine, where the MVA-BN-Filo booster dose contains EBOV, MARV, and Sudan (SUDV) virus glycoproteins (GPs) and the nucleoprotein from Tai Forest virus. While long-term immunogenicity of up to two years has been found in clinical trial settings, limited real-world data exists.  MethodsUsing a multiplexed immunoassay, samples (n=698 at baseline) collected in Mbandaka, Equateur province, DRC, between September 2023 and October 2024 were assessed for seroreactivity to six filovirus antigens (1 BDBV, 2 EBOV, 2 MARV, and 1 SUDV) at three distinct periods: baseline/pre-vaccination, 6-8 weeks post-first dose (Zabdeno), at booster administration (Mvabea), and one-year post-boost dose.  ResultsSubstantial filovirus seroreactivity was found at baseline, with 48.7% (n=340/698) of individuals being seroreactive to at least one virus antigen. High baseline seroreactivity was found against BDBV GP (31.1%, n=217/698), with lower baseline seroreactivity to EBOV GP (15.5%, n=106/698), comparatively. Overall EBOV GP seroreactivity increased to 66.8% (n=376/563) at one year-post vaccine boost and 57.6% (n=250/434) of participants were seroreactive. Despite the booster dose inclusion of SUDV GP and MARV GP, there were no substantial increases in reactivity against either antigen at subsequent timepoints. Overall filovirus seroreactivity increased at all timepoints for the entire cohort, although filovirus reactivity decreased over the study period for those who were seroreactive at baseline.  FindingsThese data highlight detection of significantly elevated seoreactivity to EBOV GP following first-dose administration of Ad26.ZEBOV, which remained relatively stable one-year post-booster dose administration. Additionally, this study identifies high levels of baseline seroreactivity to BDBV GP despite no previous documented outbreaks in this region of DRC. These data suggest that vaccination with the Ad26.ZEBOV-MVA-BN-Filo vaccine induces stable seroreactivity against EBOV GP, but not to other filovirus antigens.
ER  -