Identification of early gene expression profiles associated with long-lasting antibody responses to the Ebola vaccine Ad26.ZEBOV/MVA-BN-Filo

Computational mining of B cell receptor repertoires reveals antigen-specific and convergent responses to Ebola vaccination

“…The post-dose 1 B-cell repertoire signature is indicative of clonal expansion and class switching consistent with a plasmablast peak. There was a notable lack of these signatures following the MVA-BN-Filo dose 2, which is consistent with transcriptomic data in which genes related to B cell activation that are clearly upregulated seven days after the Ad26.ZEBOV dose 1 are not significantly upregulated (relative to baseline) following the MVA-BN-Filo dose 2 ( 54 ).…”

“…The most exceptional publicity we observed was in the 6666-like lineage, which was within the 100 largest clonotype post-boost in 32 participants, and which we had already noted as the most public lineage of antibodies in our reference database. An increase in IGHV3–15 frequency was observed by BCR-seq in primary vaccination with ERVEBO by Erhardt and colleagues ( 32 ) as well as via RNA-seq by Blengio and colleagues ( 54 ). IGHV3–15 thus plays a clear role in the B cell response to Ebolavirus vaccination, from its abundance in monoclonals isolated from at least fifteen EVD survivors and vaccinees, to its appearance in bulk BCR-seq data in both our own Ad26.ZEBOV/MVA-BN-Filo cohort and Erhardt and colleague’s ERVEBO cohort, and finally in bulk RNA-seq data.…”

Refined innate plasma signature after rVSVΔG-ZEBOV-GP immunization is shared among adult cohorts in Europe and North America

“…Previous transcriptomic analysis from blood samples of the same cohorts have shown that interferon signaling genes (ISGs) were upregulated at day 1 post-vaccination and, consistent with our results, CXCL10 was upregulated at day 1 ( 30 , 31 ). Similarly, the replication incompetent Ebola vaccine Ad26.ZEBOV increases the expression of IFN-stimulated genes (CXCL9, CXCL11, and CXCL10), and those associated with monocyte and lymphocyte recruitment such as CCL2 (MCP-1),CCL8 (MCP-2), and CCL7 (MCP-3) ( 32 ). However, compared to rVSVΔG-ZEBOV-GP, Ad26-ZEBOV combined with MVA-BN-Filo (Zabdeno/Mvabea) as well as another adenovirus-based Ebola vaccine cAd3-EBOZ is less immunogenic with less persisting antibody response, requiring higher doses to reach the same level of immunogenicity ( 33 , 34 ).…”

“…Of note, we did not detect an increase in plasma IFN protein level (similar to previous reports ( 19 )) but CXCL10 and CXCL11 increase may result from a transient and earlier IFN response before day 1. This discrepancy between gene expression and the protein level of IFN in blood might reflect rapid migration of cells to secondary lymphoid organs ( 33 ), rapid kinetics of the IFNs secretion ( 32 ) and/or a sub-optimal sensitivity of the assay used to detect these proteins. The innate vaccine response induced by the live attenuated rVSVΔG-ZEBOV-GP it is mainly related to monocyte recruitment and activation, whereas live-attenuated yellow fever mainly induces a dendritic-cell (DC) innate signature ( 35 , 36 ) and the adjuvanted influenza-H1N vaccine induces a lymphoid gene-expression signature ( 37 ).…”