Leveraging The Benefits
of Natural Immune Repertoires

Advantages of In Vivo Derived VHHs

Naive and synthetic library methods for VHH discovery 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 offer distinct advantages for the development of therapeutic VHH  candidates including:

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

By monitoring natural immune repertoires 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

Overcoming Limitations of VHH Discovery Platforms with Advanced In Vivo Strategies

Abkyu utilizes a proprietary workflow that leverages the evolving natural immune repertoires. Our process aims to first generate diverse immune response, then capture and analyze the evolving repertoires using a next generation library-based discovery workflow. 

Our proprietary workflows enable:

  • Fast identification of VHHs (60-90 days)
  • 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 
 

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

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

Boston’s In Vivo VHH Discovery Specialists

Our Services

Company

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