Helminth exposure and immune response to the two-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen

PLoS Negl Trop Dis. 2024 Apr 11;18(4):e0011500. doi: 10.1371/journal.pntd.0011500. eCollection 2024 Apr.

Abstract

Background: The exposure to parasites may influence the immune response to vaccines in endemic African countries. In this study, we aimed to assess the association between helminth exposure to the most prevalent parasitic infections, schistosomiasis, soil transmitted helminths infection and filariasis, and the Ebola virus glycoprotein (EBOV GP) antibody concentration in response to vaccination with the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen in African and European participants using samples obtained from three international clinical trials.

Methods/principal findings: We conducted a study in a subset of participants in the EBL2001, EBL2002 and EBL3001 clinical trials that evaluated the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen against EVD in children, adolescents and adults from the United Kingdom, France, Burkina Faso, Cote d'Ivoire, Kenya, Uganda and Sierra Leone. Immune markers of helminth exposure at baseline were evaluated by ELISA with three commercial kits which detect IgG antibodies against schistosome, filarial and Strongyloides antigens. Luminex technology was used to measure inflammatory and activation markers, and Th1/Th2/Th17 cytokines at baseline. The association between binding IgG antibodies specific to EBOV GP (measured on day 21 post-dose 2 and on Day 365 after the first dose respectively), and helminth exposure at baseline was evaluated using a multivariable linear regression model adjusted for age and study group. Seventy-eight (21.3%) of the 367 participants included in the study had at least one helminth positive ELISA test at baseline, with differences of prevalence between studies and an increased prevalence with age. The most frequently detected antibodies were those to Schistosoma mansoni (10.9%), followed by Acanthocheilonema viteae (9%) and then Strongyloides ratti (7.9%). Among the 41 immunological analytes tested, five were significantly (p < .003) lower in participants with at least one positive helminth ELISA test result: CCL2/MCP1, FGFbasic, IL-7, IL-13 and CCL11/Eotaxin compared to participants with negative helminth ELISA tests. No significant association was found with EBOV-GP specific antibody concentration at 21 days post-dose 2, or at 365 days post-dose 1, adjusted for age group, study, and the presence of any helminth antibodies at baseline.

Conclusions/significance: No clear association was found between immune markers of helminth exposure as measured by ELISA and post-vaccination response to the Ebola Ad26.ZEBOV/ MVA-BN-Filo vaccine regimen.

Trial registration: NCT02416453, NCT02564523, NCT02509494. ClinicalTrials.gov.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Africa
  • Aged
  • Animals
  • Antibodies, Helminth / blood
  • Antibodies, Viral* / blood
  • Child
  • Child, Preschool
  • Cytokines / immunology
  • Ebola Vaccines* / administration & dosage
  • Ebola Vaccines* / immunology
  • Ebolavirus / genetics
  • Ebolavirus / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Helminthiasis / immunology
  • Helminthiasis / prevention & control
  • Helminths / genetics
  • Helminths / immunology
  • Hemorrhagic Fever, Ebola* / immunology
  • Hemorrhagic Fever, Ebola* / prevention & control
  • Humans
  • Immunoglobulin G / blood
  • Male
  • Middle Aged
  • Young Adult

Substances

  • Antibodies, Helminth
  • Antibodies, Viral
  • Cytokines
  • Ebola Vaccines
  • Immunoglobulin G

Associated data

  • ClinicalTrials.gov/NCT02509494
  • ClinicalTrials.gov/NCT02416453
  • ClinicalTrials.gov/NCT02564523

Grants and funding

This work was an ancillary study undertaken within the framework of the EBOVAC2 project, which was funded by the Innovative Medicine Initiative (IMI) (http://www.imi.europa.eu/). This is a European Union programme (Grant number 115861). The present work is part of a PhD programme within the EBOVAC2 project (Grant number 115861). The PhD budget was already allocated to HB's home institution (Centre MURAZ), which is a member of the consortium put in place to implement the project and conduct a phase 2 trial of the Ad26ZEBOV/MVA-BN-Filo vaccine in Europe and Africa. Both HB and RT, the student and the director of the thesis have actively participated in the implementation of the Project in Africa and Europe. The present work used some data from the EBOVAC1 (Grant number 115854) project but did not receive direct funding from this grant. The funder (IMI) had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.