The preparation of single domain antibody libraries starting from lymphocytes recovered from immunized members of the Camelidae enables to collect binders that underwent somatic maturation. However, the time and costs necessary to prepare a library for each new antigen may urge to look for alternatives such as those offered by large one-pot libraries.
Here we constructed thirteen large naïve libraries using PBMCs and spleens from 65 healthy nonimmunized Alpacas.The library consists of more than 1011 individual transformants with more than 90% unique sequences and the positive insert ratio was more than 99.99%. We leverage this established library along with our advanced screening platform to extend the epitope coverage and help clients find the optimal monoclonal antibody candidates Despite the lack of somatic maturation, the selection based on phage display allowed to isolate from such naïve libraries VHHs with affinity in the subnanomolar range and suitable for the standard immunoapplications.