Why Protein-Level Antibody Discovery Matters

Have you ever wondered why some antibody therapies work so well while others fall short? It often comes down to how we find and select them. In this second article in our series, we'll explain why protein-level discovery is a breakthrough for Abvion and the field of antibody therapeutics.

The Challenge of Traditional Antibody Discovery

Traditional antibody discovery methods, like B-cell sequencing, have driven major advances in human antibody therapeutics. They let us sequence DNA from immune cells to reconstruct antibodies. But there's a catch: these methods rely on accessing B cells, mostly in blood or tissues like the spleen.

Most antibodies, however, are produced by long-lived plasma cells in the bone marrow. These are hard to reach without very invasive procedures. Typical approaches, therefore, focus on circulating memory B cells, using genetic sequences of their B-cell receptors (BCRs) as proxies for functional antibodies. This can miss the full picture. For example, B-cell sequences do not necessarily correspond to circulating antibodies, and they don't capture quantitative details like abundance or the polyclonal context.

In our experience, this means we might overlook the most mature, battle-tested antibodies that the body has selected for large-scale production. These limitations highlight the need for a more direct approach. Protein-level discovery analyzes the antibodies themselves in serum or plasma, giving us the immune system's "final product”.

The most optimized and matured antibodies are found at the protein level.

Why Protein-Level Discovery Matters

Protein-level discovery shifts the focus from cells and genetic proxies to circulating antibodies themselves – the active molecules at work in the body. At Abvion, our serological antibody discovery platform uses proteomics to capture these antibodies with high fidelity, revealing insights that genetic methods can't. Here’s why this approach is superior:

• Capturing Mature, Functional Antibodies: We analyze antibodies in their final, optimized state, fully matured through natural selection. This ensures we're working with proven, effective molecules, not just genetic blueprints.

• Quantitative and Polyclonal Insights: Unlike B-cell sequencing, we measure the abundance of antibodies and their polyclonal context, uncovering details that may boost therapeutic potential.

• Scalability and Accessibility: It requires only small serum samples from biobanks, making it ideal for large-scale studies and rapid deployment – perfect for responding to pandemics or rare diseases.

In prof Albert Heck's lab at Utrecht University, our founding team observed firsthand how protein-level analysis revealed antibodies and molecular details that genetic analyses simply overlooked. This insight inspired the founding of Abvion, where we're turning it into a standalone platform that doesn't need orthogonal data like B-cell sequencing. It handles complex samples with minimal input, delivering more accurate, protein-derived sequences.

Abvion's Platform in Action

Our platform is designed to make protein-level discovery practical for biopharma applications. It identifies exceptional human antibodies with unmatched precision, including those from hard-to-reach plasma cells. This leads to diverse candidates that are safer and more effective, as they're already optimized by the human body.

We're already applying our technologies in pilots for infectious diseases and autoimmunity, teaming up with both biopharma and academia. These collaborations show the platform's versatility – identifying panels with potent human antibodies without requiring any additional tools.

Looking Ahead

Protein-level discovery is the foundation of Abvion's mission to create superior antibody therapeutics. In the next article, Sem Tamara, our Head of Discovery Technologies, will explore how mass spectrometry makes this possible.

In the meantime, be sure to follow us on LinkedIn to stay up to date on our latest progress.

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