Custom Single Domain Antibody (SdAb) Library Generation Services

Q: How is a custom VHH library generated?

VHH library construction involves multiple steps. Researchers often start by immunizing camelids (such as llamas or alpacas) with the target antigen. The genes that encode the VHHs are then amplified utilizing procedures such as PCR. These amplified sequences are cloned into vectors to form a uniformed library. This library can be screened to isolate VHHs with high affinity and specificity to the target antigen.

Three strategies of Custom sdAb Library Case Study Published Data FAQ Resources

As a pioneer and undisputed global leader in the field of sdAb development, Creative Biolabs is professional in applying our custom strategies to satisfy various V_HH library demands. With our extensive experience and advanced library construction platform, we are confident in offering custom V_HH library services to meet our customers' different objectives and guarantee the most satisfactory results for clients worldwide.

Custom V_HH Library at Creative Biolabs

The field of V_HH has rapidly progressed over the last two decades, mainly because of the interest in their human therapeutic and diagnostic applications. To identify practical V_HHs, it is essential to start with a high-quality gene bank of V_HHs, dedicated to the final application and with maximal diversity. Currently, our seasoned scientists have set up a series of strategies that can assist in generating custom V_HH libraries with the highest efficiency and best quality. Our powerful strategies include:

Naïve V_HH Library

No animal immunization
Larger library size
Explicitly unbiased nature of the V_HH repertoires
Capable of generating sdAbs against any specific targets

Immune V_HH Library

Immunization
Only require a handful of materials
Somatic maturation in vivo
Highly enrichment of target specific V_HH with high affinity

Synthetic V_HH Library

Various design strategies are available
High diversity and utility
Capable of generating V_HH against any specific targets
Extensively used in the industry

First of all, retrieval of V_HHs from an immune library is a priority consideration. Creative Biolabs has unparalleled capabilities for the construction of V_HH or VNAR based V_HH libraries through immunized camel, llama, alpaca, or shark, thanks to our advanced technology. The immune V_HH library is unique because it provides access to intact, affinity-matured, antigen-binding fragments. Somatic maturation in lymphocytes of immunized animals results in V_HH libraries with greater specificity and higher affinity for antigens of interest. Among all species of immune libraries, llamas and alpacas are often used because they are smaller in size (making them easier to raise and breed) and are commonly found in European and American markets. V_HHs from these animals are considered well-suited for therapeutic purposes. In contrast, camel serum has a higher content of V_HHs, with more abundant antibody germline and additional disulfide bonds. These features suggest that camel libraries may be more suitable for applications requiring more stable V_HHs, such as diagnostic affinity reagents.

Alternatively, a suitable naïve V_HH library or even a synthetic V_HH library can be used to identify antigen binders in cases where immunization is difficult, the antigen is lacking or low in immunogenicity. Although naïve libraries and synthetic V_HH libraries require larger libraries to retrieve specific binders of high affinity, such diversified V_HH libraries enable the selection of antibody fragments specific to virtually any target.

Equipped with advanced platforms and powerful technologies, Creative Biolabs is proud to tailor and conduct the best-fit proposal to meet our customers' specific V_HH library requirements. Contact us to learn how we can help you generate a custom V_HH library.

Published Data

The Construction of the Anti-HIV Envelope Glycoprotein V_HH Library

Fig. 1 Inhibition of sCD4-gp120 Interaction by Selected V_HHs.¹

This article introduces a novel approach to the construction of a family-specific phage library of single-chain antibody fragments (V_HH) derived from llamas, which are capable of competitively binding to the HIV-1 envelope glycoprotein. Researchers employed biopanning and ELISA experiments to identify V_HHs with high affinity, subsequently analyzing their binding characteristics to HIV-1 via surface plasmon resonance (SPR) technology. The results demonstrate that these V_HH exhibit broad neutralizing activity against different HIV-1 subtypes, with specific amino acids in the CDR3 loop being crucial for their neutralizing capacity. These findings provide an effective and efficient way of generating a V_HH library, offering novel strategies for the development of efficacious HIV-1 vaccines.

Reference

Koh, Willie WL, et al. "Generation of a family-specific phage library of llama single chain antibody fragments that neutralize HIV-1." Journal of Biological Chemistry 285.25 (2010): 19116-19124. Distributed under Open Access license CC BY 4.0, without modification.

FAQ

1. How is a custom V_HH library generated?

V_HH library construction involves multiple steps. Researchers often start by immunizing camelids (such as llamas or alpacas) with the target antigen. The genes that encode the V_HHs are then amplified utilizing procedures such as PCR. These amplified sequences are cloned into vectors to form a uniformed library. This library can be screened to isolate V_HHs with high affinity and specificity to the target antigen.