Leveraging The Benefits
of Natural Immune Repertoires

Traditionally, library based approaches have been used to discover VHHs. These methods are well established but can produce antibodies with low affinities,  unfavorable developability profiles, and challenges for screening in cell-based contexts. In vivo based discovery methods have the ability to deliver VHHs with:

  • A range of high affinities
  • Improved developability profiles and ‘drug-like’ characteristics
  • High specificity to soluble and cell based targets

By monitoring the development of the natural immune response over time, we are able identify high quality VHH leads that are best suited for our partners’ therapeutic applications.

Limitations of In Vivo VHH
Discovery Platforms

There are many in vivo-based VHH discovery approaches that begin to capture the advantages of the natural immune system. However,  these approaches have certain limitations that can affect the success of the discovery effort, including: 

  • Low screening throughput leading to clonal bias and lack of diversity
  • Reliance on serum titer, which is not representative of B cell repertoires and can rise slowly 
  • Single timepoint capture of the immune response, further limiting diversity and overall repertoire sample size

Limitations of In Vitro VHH Discovery Platforms

In vitro-based discovery approaches have been used for many years to generate VHHs. This process allows for fast capture of VHH hits but has certain limitations that become more pronounced as the applications and functional requirements of these molecules continuously evolve. These limitations include: 

  • Inability to screen against cell surface targets 
  • Poor affinity and developability of hits, requiring further engineering efforts
  • Process attrition and realized diversity
  • Business terms and FTO

Abkyu utilizes a proprietary workflow that leverages next generation sequencing of target-specific B cells over the evolving immune response to identify the best possible leads for our partners’ downstream applications.

Iterative sequencing and empirical testing allow us to build high confidence sequence selection models that enable:

  • Fast identification of VHHs as they appear in the immune response 
  • Expanded sequence and functional diversity
  • Discovery of naturally derived VHHs with improved affinity, specificity, and developability profiles 
  • Generation of fully owned antigen specific VHH sequence and cDNA archives 
Using deep NGS sequencing and empirical testing, we are able to mine natural immune responses and build predictive sequence selection models to efficiently nominate VHHs with therapeutic potential. 
 

Working With Abkyu

De-Risked Discovery

Custom immunization protocols and adjuvant strategies to ensure tailored immune responses

Deep repertoire sequencing and archiving of millions of antigen specific B cells

Machine learning and bioinformatics pipeline for thorough interrogation of VHH repertoire

Scientific Collaboration

Transparency and collaboration in everything we do

Regular data and project communications so our partners know exactly what is going on in their projects

Fully owned partner deliverables enable open access to project data

Expertise and Specialization

Leverage optimized camelid immunization protocols to achieve precise and effective immune responses

Custom VHH bioinformatics pipelines designed to address intricacies of camelid immune system and VHH molecules

Lead characterization pipelines designed to test VHHs for relevant downstream applications

Contact us to discuss your next VHH project