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Early emergence of signatures associated with HCV infection outcome

2026 Immcantation Users Group Meeting https://immcantation.github.io/users-... Title: Early emergence of signatures associated with HCV infection outcom e Speaker: Money Gupta, University of New South Wales (AU) Abstract: Previous studies have demonstrated a delayed emergence of neutralising antibodies (nAbs) as a biomarker of failure to clear hepatitis C virus (HCV) infection, but why this happened remains unclear. Here in this study we examined whether the B cell repertoire of the HCV Transmission Founder (TF) virus was associated with this delay in the nAb development in a unique cohort of acute primary HCV infected individuals that were followed over time. TF variants from subjects that developed clearance had early formation of memory B cells and were more resistant to broadly neutralising antibodies (BnAbs). NAbs that appeared in subjects that did not clear the infection, we observed higher utilization of Vh1-69, Vh1-18 genes and somatic hypermutation (SHM) in chronics, and longer complementarity-determining region 3 (CDR3) regions in the B cell heavy chain suggesting additional rounds of maturation might be required to achieve strong binding against chronic TF variants. We used Change-O implemented in Immcantation for identification of clones and SHM in B cell repertoire, and no clonal differences were found across the outcome. This study observed a negative correlation of SHM with CDR3 whereas, an increase in the binding affinity with the increase in SHM. Transcriptomic analysis of the E2-specific memory B cells showed a distinct population within memory B cells that can be found in other infections well, and no pathway differences were found across the outcome. Finally, this work showed the relevance of identifying antibodies that can be effective vaccine targets to B cell germlines and can drive early differences in nAb development, and possibly enhance antigen valency for the development of HCV vaccines.