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

Abstract

AbstractBackgroundThe 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 FindingsWe 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 andStrongyloidesantigens. 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 toSchistosoma mansoni(10.9%), followed byAcanthocheilonema viteae(9%) and thenStrongyloides 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/SignificanceNo 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.Author SummaryRecurrent exposure to parasites may influence the immune response to vaccines, especially in endemic African countries. In this study we aimed to assess the association between immune markers of helminth exposure and the immune response post-vaccination with the Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen in African and European participants who participated in three international clinical trials. Seventy-eight (21.3%) of the 367 participants included in the study, had at least one helminth ELISA positive test at baseline with differences of prevalence between studies and an increased prevalence with increasing age. After adjustment for confounding factors, the study did not show a clear association between immunological markers of helminth exposure and the antibody concentration in response to the Ebola vaccine regimen.