Long-term cellular immunity of vaccines for Zaire Ebola Virus Diseases

Affiliations
  • 1Vaccine Research Institute, Université Paris-Est, Créteil, France.
  • 2INSERM U955, Institut Mondor de Recherche Biomedicale (IMRB), Team Lévy, Créteil, France.
  • 3Univ. Bordeaux, INSERM, Institut Bergonié, CHU de Bordeaux, CIC-EC 1401, Euclid/F-CRIN clinical trials platform, Bordeaux, France.
  • 4Univ. Bordeaux, Inserm, Population Health Research Center, UMR 1219, INRIA SISTM, Bordeaux, France.
  • 5Alliance for International Medical Action, Dakar, Senegal.
  • 6Centre National de Formation et de Recherche en Santé Rurale (CNFRSR), Maferinyah, Guinea.
  • 7Vaccine Research Institute, Université Paris-Est, Créteil, France. yves.levy@aphp.fr.
  • 8INSERM U955, Institut Mondor de Recherche Biomedicale (IMRB), Team Lévy, Créteil, France. yves.levy@aphp.fr.
  • 9Assistance Publique-Hôpitaux de Paris, Groupe Henri-Mondor Albert-Chenevier, Service Immunologie Clinique, Créteil, France. yves.levy@aphp.fr.

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Abstract

Recent Ebola outbreaks underscore the importance of continuous prevention and disease control efforts. Authorized vaccines include Merck’s Ervebo (rVSV-ZEBOV) and Johnson & Johnson’s two-dose combination (Ad26.ZEBOV/MVA-BN-Filo). Here, in a five-year follow-up of the PREVAC randomized trial (NCT02876328), we report the results of the immunology ancillary study of the trial. The primary endpoint is to evaluate long-term memory T-cell responses induced by three vaccine regimens: Ad26-MVA, rVSV, and rVSV-booster. Polyfunctional EBOV-specific CD4 T-cell responses increase after Ad26 priming and are further boosted by MVA, whereas minimal responses are observed in the rVSV groups, declining after one year. In-vitro expansion for eight days show sustained EBOV-specific T-cell responses for up to 60 months post-prime vaccination with both Ad26-MVA and rVSV, with no decline. Cytokine production analysis identify shared biomarkers between the Ad26-MVA and rVSV groups. In secondary endpoint, we observed an elevation of pro-inflammatory cytokines at Day 7 in the rVSV group. Finally, we establish a correlation between EBOV-specific T-cell responses and anti-EBOV IgG responses. Our findings can guide booster vaccination recommendations and help identify populations likely to benefit from revaccination.

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