Prediction and characterisation of the human B cell response to a heterologous two-dose Ebola vaccine

Given the increasing Ebola virus disease (EVD) outbreaks and the critical importance of protecting frontline health workers, this study comprehensively characterizes the human B cell immune responses elicited by the heterologous two-dose Ebola vaccine regimen of Ad26.ZEBOV (prime) and MVA-BN-Filo (boost). Utilizing single-cell RNA-sequencing and ELISpot assays, the research revealed robust plasma cell and lasting B cell memory responses post-vaccination. Total IgG-secreting plasma cell (IgG-ASC) frequencies peaked at days 9-11 post-prime and days 5-7 post-boost, correlating with extensive differential gene regulation, particularly of immunoglobulin gene segments. Memory B cell (BMEM) responses were observed after the first dose and significantly enhanced by the second, persisting for over four years post-vaccination with minimal waning. A unique B cell receptor CDRH3 sequence, resembling Orthoebolavirus zairense (EBOV) glycoprotein-binding antibodies, was detected exclusively post-vaccination. Notably, machine-learning models trained on early blood gene expression successfully predicted the magnitude of subsequent antibody responses, identifying key genes such as IGHV3-15, associated with EBOV-GP binding antibodies. These findings underscore the predictive utility of early immune responses and provide crucial mechanistic insights for future EVD preparedness strategies.
(MKO)