Profile of the B cell receptor repertoire and antibody responses upon 17DD-YF vaccine boosting

Although the 17DD-YF vaccine is highly effective in conferring long-term immunity, recent studies suggest that booster doses may be necessary in endemic areas. In this study, we characterized the dynamics of the B cell repertoire following 17DD-YF booster vaccination and examined its impact on antibody kinetics. Using a combined approach of serological analysis and B cell receptor (BCR) sequencing, we investigated molecular features of the antibody response in four vaccinated individuals from a YFV-endemic region. Our results indicate that the booster induces a transient antibody response, with limited effect on the neutralization capacity against DENV1-4 and ZIKV. Notably, we observed a rapid clonal expansion of B cells within 14 days post-vaccination, predominantly involving IgA and IgG isotypes. However, this expansion was short-lived, with reduced magnitude and persistence of these lineages by day 28. Interestingly, some of the expanded lineages shared sequence similarity with previously characterized anti-DENV and anti-ZIKV antibodies, although further validation is required to assess their functional relevance and presence in circulating serum. Together, these findings highlight the transient nature and isotype composition of the antibody response following YFV revaccination and provide insights into the complex interplay between pre-existing immunity and recall responses in individuals living in endemic regions.