Immunized vs naïve libraries

When generating nanobodies, researchers often utilize libraries of antibody fragments. These libraries can be broadly categorized into two types: immunized and naïve libraries.

Why use immunized library service?

Nanobody library is typically generated from nanobody genes isolated from the PBMC of the immunized donors to clone the antigen-specific nanobody in a phage display vector. As nanobody repertories usually undergo in vivo affinity maturation processes during the immunization process, the nanobodies derived from the immune library will generally possess higher affinities and specificities toward the antigens of interest if compared to those obtained from the naïve library. The immune repertoires are used to isolate distinct nanobodies against particular antigens, e.g., cell surface antigens of pathogen or tumor markers.

The benefits of using nanonody immunized library service include:

  • More likely to obtain desired nanobodies against particular antigens
  • Able to recognize novel epitopes
  • Greater affinity and specificity

Why use naïve library service?

Naïve nanobody phage library is a valid alternative to the immunized nanobody phage library, and in light of the short turn-around time, the naïve nanobody library is by far the most used strategy for the selection of new antibodies. Naïve libraries are especially recommended for antigens with low immunogenicity, toxic, lethal, transmissible effects, or nonimmunogenic small molecular compounds.

The benefits of using nanobody naïve library service include:

  • Reduced lead times
  • Overcome immunogenicity issues
  • Minimization of animal use (no animal immunization is required)
  • Possibility of using the same antibody library in different projects (versatility)
Immunized libraries Naïve libraries
Species Camelids and sharks Camelids and sharks
Number of binders Higher High
Affinity of binders Higher High
Potential immunogenicity issues Yes No
Animal use Yes No
Timelines 5~6 months (Camelids) 6.5~8.5 months (Sharks) 1.5~2 months