Deciphering cynomolgus macaque IGLV genes after ZIKV-E immunization and viral challenge 4191

Abstract Description Antibody immune receptor repertoire (AIRR) analysis is essential for understanding antibody-mediated immune responses. AIRR analysis plays a key role in advancing vaccine designs and developing therapeutic monoclonal antibodies (mAbs). While Cynomolgus macaques are important immunological models, the lack of databases for Cynomolgus macaque immunoglobulin lambda chain variable (IGLV) genes hinders comprehensive repertoire analyses. In this study, we conducted single-cell sequencing of two cynomolgus macaques at two time points following immunization with Zika virus envelope protein (ZIKV-E). Unexpectedly, we observed a predominant usage of lambda chain genes, contrasting with the expected kappa chain dominance. We found that cynomolgus IGLV genes do not align well with rhesus or human databases due to significant genetic divergence. Our analysis also reveals longitudinal convergence in IGLV usage after ZIKV-E immunization. Additionally, we identified novel IGLV and IGLD sequences unique to cynomolgus macaques. Recombinant expression of ZIKV-E-specific mAbs confirmed reactivity and neutralization, validating the functional relevance of these IGLV genes. Lastly, we developed a putative map of the IGLV loci in cynomolgus macaques to facilitate future analyses. In conclusion, our findings provide critical resources and insights into cynomolgus macaque IGLV genes to enhance vaccine and therapeutic developments against critical diseases. Funding Sources This project was supported by grants from the National Science Foundation (NSF), award #2300976, and the National Institutes of Health (NIH), National Institute of General Medical Sciences (NIGMS), IDeA Networks of Biomedical Research Excellence (IMBRE), Award number: P20GM103466. The content is solely the responsibility of the authors and do not necassarily represent the official view of the NSF. Topic Categories Vaccines and Immunotherapy (VAC)