rVSV-ZEBOV vaccination in people with pre-existing immunity to Ebolavirus: an open-label safety and immunogenicity study in Guinean communities affected by Ebola virus disease (l'essai proches).

Conall H Watson ; Pierre-Stéphane Gsell ; Yper Hall ; Anton Camacho ; Ximena Riveros ; Godwin Enwere ; Andrea Vicari ; Séverine Danmadji Nadlaou ; Alhassane Toure ; Ismaila M Sani ; +27 more... Abdourahamane Diallo ; Cece Kolie ; Sophie Duraffour ; Kékoura Ifono ; Andre Maomou ; Kassie Dore ; Honora A Djidonou ; Aminata Bagayoko ; Philos P Damey ; Mabetty Nancy Camara ; Fatoumata Battouly Diallo ; Fofana Thierno Oumar ; Kalidou Toure ; Mohamed Lamine Diaby ; Lansana Sylla ; Doussou Conde ; Ibrahima Lansana Kaba ; Tom Tipton ; Rosalind M Eggo ORCID logo ; Michael Marks ORCID logo ; Chrissy H Roberts ORCID logo ; Thomas Strecker ; Stephan Günther ; Sakoba Keita ; W John Edmunds ORCID logo ; Miles W Carroll ; Ana Maria Henao-Restrepo ; (2024) rVSV-ZEBOV vaccination in people with pre-existing immunity to Ebolavirus: an open-label safety and immunogenicity study in Guinean communities affected by Ebola virus disease (l'essai proches). BMC medicine, 22 (1). 523-. ISSN 1741-7015 DOI: 10.1186/s12916-024-03726-z
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BACKGROUND: Zaire Ebolavirus disease (EVD) outbreaks can be controlled using rVSV-ZEBOV vaccination and other public health measures. People in high-risk areas may have pre-existing antibodies from asymptomatic Ebolavirus exposure that might affect response to rVSV-ZEBOV. Therefore, we assessed the impact pre-existing immunity had on post-vaccination IgG titre, virus neutralisation, and reactogenicity following vaccination. METHODS: In this prospective cohort study, 2115 consenting close contacts ("proches") of EVD survivors were recruited. Proches were vaccinated with rVSV-ZEBOV and followed up for 28 days for safety and immunogenicity. Anti-GP IgG titre at baseline and day 28 was assessed by ELISA. Samples from a representative subset were evaluated using live virus neutralisation. RESULTS: Ten percent were seropositive at baseline. At day 28, IgG in baseline seronegative (GMT 0.106 IU/ml, 95% CI: 0.100 to 0.113) and seropositive (GMT 0.237 IU/ml, 0.210 to 0.267) participants significantly increased from baseline (both p < 0.0001). There was strong correlation between antibody titres and virus neutralisation in day 28 samples (Spearman's rho 0.75). Vaccinees with baseline IgG antibodies against Zaire Ebolavirus had similar safety profiles to those without detectable antibodies (63.6% vs 66.1% adults experienced any adverse event; 49.1% vs 60.9% in children), with almost all adverse events graded as mild. No serious adverse events were attributed to vaccination. No EVD survivors tested positive for Ebolavirus by RT-PCR. CONCLUSIONS: These data add further evidence of rVSV-ZEBOV safety and immunogenicity, including in people with pre-existing antibodies from suspected natural ZEBOV infection whose state does not blunt rVSV-ZEBOV immune response. Pre-vaccination serological screening is not required.


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