At the end of September, I had the opportunity to present at the 4th Single-Domain Antibody (sdAb/VHH) Conference hosted in the city of Utrecht. The sdAb conference is a biennial event, and was held for the first time in Bonn (2019), then in Brussels (2021) and Paris (2023), before coming to the Netherlands this year.

This was the first time I’d attended a VHH-focused conference, and I was taken aback at just how large the community is; the Jaarbeurs ‘Supernova’ event hall was completely sold out, with over 400 researchers in attendance (pictures below courtesy of the organisers). The buzz reflects the ever growing interest in sdAbs as tools to discover new fundamental biology, vectors for diagnosing disease, and as prophylactic or curative therapeutics. Most every disease indication was represented at the conference, from anticancer and antiviral sdAbs to antivenom sdAbs (both for use in lateral flow tests to diagnose the snake that bit you, and as quick ‘epipen’-like therapeutics accessible even in the most remote parts of the world).

I was delighted to share (now Dr.!) Gemma Gordon’s work on the Therapeutic Nanobody Profiler (“TNP”, preprint here, webapp here), adapting our established Therapeutic Antibody Profiler (TAP) framework to cover this emerging modality of adaptive immune receptor. I also highlighted OPIG’s growing suite of resources for sdAb science, in particular our databases, which now cover searching for solved structures of sdAbs (SAbDab-nano), molecular data on therapeutic sdAbs (Thera-SAbDab), patented and literature-reported sdAbs (PLAbDab-nano), and natural sdAb receptor repertoire sequencing datasets (Unpaired OAS — with more VHH repertoire samples coming soon!). Other computational talks were given by Dr. Joe Watson on how Xaira Therapeutics are using the latest generative machine learning methods to guide the design of novel sdAbs, and from Dr. Aubin Ramon from the Sormanni group on their fantastic AbNativ and Nanomelt software packages.

Unfortunately, I could only attend the first half of the conference (all hands on deck at the Doctoral Training Centre for the start of the academic year!), but my three key take-homes from the sessions I attend were:

1. Immunised-camelid libraries still hold sway over synthetic VHH libraries: time and again, people were reporting that, in their experience, immunised-animal libraries seemed to yield the best-behaved sdAbs, although there was a strong belief that synthetic libraries could and would be improved in time through rational design.

2. Rational affinity tuning methods are in high demand: the desire for methods that could guide engineering to tune down (as well as dial up) affinity was reiterated, whether these sdAbs were to be used as multispecific ‘logic gate’ activity switches or as dynamic molecular sensors. Accurate affinity prediction remains a challenging task for all adaptive immune receptors, but improvements would have a big impact on sdAb science.

3. Computational methods are under-utilised across sdAb science, but there’s a groundswell of excitement to try them out: I was told by several attendees that the number of computational talks had grown significantly at this meeting relative to the last. Many would like to develop new computational methods with their data, but lack experience with software engineering/machine learning. I would encourage more dry-lab scientists to bookmark this conference for 2027, as there are ample collaboration opportunities just waiting to be explored.

I also want to highlight the Nanosaurus effort (https://nanobodies.vib.be/) by a consortium of high-profile researchers (hosted by the VIB in Belgium), as a companion resource to our PLAbDab-Nano database. Nanosaurus is an independent attempt to document characterised sdAbs, and accepts direct community submissions.

This conference came at an opportune time, as my own research interests are starting to bend towards sdAb science (shout out to new OPIGlets Clare and Nathan who will be working on these projects!), and it was great to get such a holistic refresher on the field. Huge thanks to the organisers (especially Drs. Raymond Heukers and Sabrina Oliveira) for covering all my expenses and putting on such a slick event with amazing networking opportunities, ample chance to assess and engage with the posters and speakers, and wonderful dinners.

And I must also extend my thanks to Henriette, who, as an Utrecht native, gave me so many tips on things to do and places to eat that I turned up in a new city feeling like a local. Strongly recommend a trip to Utrecht if you’re ever in the area; it’s an intriguing blend of heritage (lovely old canals with adjacent restaurants) and seriously impressive urban planning.