Innate and cellular immune response to the Ebola vaccine Ad26.ZEBOV, MVA-BN-Filo: an ancillary study of the EBL2001 phase II trial

Christine Lacabaratz; Mélany Durand; Aurélie Wiedemann; Emile Foucat; Mathieu Surénaud; Corinne Krief; Lydia Guillaumat; Cynthia Robinson; Kerstin Luhn; Viki Bockstal; Rodolphe Thiébaut; Laura Richert; Yves Lévy

doi:10.1093/infdis/jiae360

Innate and cellular immune response to the Ebola vaccine Ad26.ZEBOV, MVA-BN-Filo: an ancillary study of the EBL2001 phase II trial

J Infect Dis. 2024 Jul 16:jiae360. doi: 10.1093/infdis/jiae360. Online ahead of print.

Authors

Christine Lacabaratz^{1

2

3}, Mélany Durand^{1

4}, Aurélie Wiedemann^{1

2

3}, Emile Foucat^{1

2

3}, Mathieu Surénaud^{1

2

3}, Corinne Krief^{1

2

3}, Lydia Guillaumat^{1

2

3}, Cynthia Robinson⁵, Kerstin Luhn⁵, Viki Bockstal⁵, Rodolphe Thiébaut^{1

4

6}, Laura Richert^{1

4

6}, Yves Lévy^{1

2

3

7}

Affiliations

¹ Vaccine Research Institute-VRI, France.
² INSERM Unité U955, IMRB, Créteil, France.
³ Université Paris-Est, Faculté de Médecine, Créteil, France.
⁴ Univ. Bordeaux, Inserm, Population Health Research Center, UMR 1219, INRIA SISTM, Bordeaux, France.
⁵ Janssen Vaccines and Prevention, Leiden, The Netherlands.
⁶ CHU Bordeaux, Department of medical information and CIC-EC 1401/Euclid F-CRIN, Bordeaux, France.
⁷ Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Henri-Mondor Albert-Chenevier, service d'immunologie clinique, Créteil, France.

PMID: 39012798
DOI: 10.1093/infdis/jiae360

Abstract

Background: The EBL2001 phase 2 trial tested the two-dose Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine in Europe. Safety and humoral immunogenicity assessments led to EU market authorization in 2020. Complementary analyses of immune responses are warranted to better characterize vaccine effects.

Methods: We conducted an ancillary study to analyze changes in the serum and cellular responses. Serum biomarkers of activation/inflammation were evaluated using a Luminex assay. Vaccine-elicited T cell responses and functions were evaluated assessing their phenotype, cytokine production, proliferation and cytotoxic potential. Integrated data analysis was performed through correlation and principal component analysis of serum biomarkers and cellular immune responses.

Results: Forty-eight volunteers were included. The Ad26.ZEBOV, MVA-BN-Filo vaccine elicited: i) serum increase of inflammatory/activation markers mainly at 1 day after the Ad26.ZEBOV vaccine; ii) durable EBOV-specific T cell proliferation and CD8+ T cells exhibiting a cytotoxic phenotype after Ad26.ZEBOV prime, after MVA-BN-Filo boost and 6 months post vaccination. Integrated analysis revealed correlations between: i) EBOV-specific CD8+ T cell proliferation and cytotoxic phenotype; ii) high EBOV-specific CD8+ T cell cytotoxic phenotype and low inflammatory marker IL-8 at day 1 post vaccination.

Discussion: This study provides unique insights into the in vivo contribution of proliferation/cytotoxic CD8+ T cells and inflammation to the Ad26.ZEBOV, MVA-BN-Filo vaccine-induced potency.

Keywords: EBOLA; T cell responses; antibody; biomarkers; vaccine immunogenicity.

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