The Effect of Previous Exposure to Malaria Infection and Clinical Malaria Episodes on the Immune Response to the Two-Dose Ad26.ZEBOV, MVA-BN-Filo Ebola Vaccine Regimen
Author:
Manno Daniela1, Patterson Catriona1, Drammeh Abdoulie12, Tetteh Kevin1, Kroma Mattu Tehtor23, Otieno Godfrey Tuda12, Lawal Bolarinde Joseph12, Soremekun Seyi1, Ayieko Philip14, Gaddah Auguste5, Kamara Abu Bakarr23, Baiden Frank12, Afolabi Muhammed Olanrewaju12ORCID, Tindanbil Daniel12, Owusu-Kyei Kwabena12, Ishola David12, Deen Gibrilla Fadlu3, Keshinro Babajide6ORCID, Njie Yusupha12, Samai Mohamed3, Lowe Brett17, Robinson Cynthia6, Leigh Bailah3, Drakeley Chris1, Greenwood Brian1, Watson-Jones Deborah14
Affiliation:
1. London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK 2. EBOVAC Project Office, Kukuna Road, Kambia, Sierra Leone 3. College of Medicine and Allied Health Sciences, University of Sierra Leone, New England Ville, Freetown, Sierra Leone 4. Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza P.O. Box 11936, Tanzania 5. Janssen Research and Development, 2340 Beerse, Belgium 6. Janssen Vaccines and Prevention, 2333 CB Leiden, The Netherlands 7. KEMRI-Wellcome Trust Research Programme, Kilifi P.O. Box 230, Kenya
Abstract
We assessed whether the immunogenicity of the two-dose Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen with a 56-day interval between doses was affected by exposure to malaria before dose 1 vaccination and by clinical episodes of malaria in the period immediately after dose 1 and after dose 2 vaccinations. Previous malaria exposure in participants in an Ebola vaccine trial in Sierra Leone (ClinicalTrials.gov: NCT02509494) was classified as low, intermediate, and high according to their antibody responses to a panel of Plasmodium falciparum antigens detected using a Luminex MAGPIX platform. Clinical malaria episodes after vaccinations were recorded as part of the trial safety monitoring. Binding antibody responses against the Ebola virus (EBOV) glycoprotein (GP) were measured 57 days post dose 1 and 21 days post dose 2 by ELISA and summarized as Geometric Mean Concentrations (GMCs). Geometric Mean Ratios (GMRs) were used to compare groups with different levels of exposure to malaria. Overall, 587 participants, comprising 188 (32%) adults (aged ≥ 18 years) and 399 (68%) children (aged 1–3, 4–11, and 12–17 years), were included in the analysis. There was no evidence that the anti-EBOV-GP antibody GMCs post dose 1 and post dose 2 differed between categories of previous malaria exposure. There was weak evidence that the GMC at 57 days post dose 1 was lower in participants who had had at least one episode of clinical malaria post dose 1 compared to participants with no diagnosed clinical malaria in the same period (GMR = 0.82, 95% CI: 0.69–0.98, p-value = 0.02). However, GMC post dose 2 was not reduced in participants who experienced clinical malaria post-dose 1 and/or post-dose 2 vaccinations. In conclusion, the Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen is immunogenic in individuals with previous exposure to malaria and in those who experience clinical malaria after vaccination. This vaccine regimen is suitable for prophylaxis against Ebola virus disease in malaria-endemic regions.
Funder
Innovative Medicines Initiative European Union’s Horizon 2020 research and innovation program European Federation of Pharmaceutical Industries and Association
Subject
Pharmacology (medical),Infectious Diseases,Drug Discovery,Pharmacology,Immunology
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