Alpaca nanobodies: how alpaca and llama antibodies are changing medicine

What sets a nanobody apart from a normal antibody

A classic antibody consists of two heavy and two light protein chains. Camelids additionally have so-called heavy-chain antibodies that lack the light chains entirely. This class of antibodies was discovered by a Belgian research team; the paper appeared in 1993 in Nature.

The single antigen-binding domain of such an antibody is called a VHH or nanobody. It weighs about 15 kilodaltons, while a complete conventional IgG antibody weighs about 150 kilodaltons. Despite this difference in size, a nanobody still recognizes its target with high specificity. That does not automatically make it better, but it opens up applications for which large antibodies are too bulky or too sensitive.

Why the tiny size is interesting for medicine

Nanobodies are robust, highly soluble and comparatively easy to produce in microorganisms. Thanks to their compact shape, they can reach clefts and binding pockets that a complete antibody has a harder time getting to. Researchers can also link several nanobodies together like building blocks. This creates a molecule that binds different sites of the same pathogen or even several targets at once.

The small size has a downside, too: a single nanobody is usually filtered out of the blood by the kidneys faster than a large antibody. For drugs, its residence time therefore often has to be extended deliberately, for example by coupling it to further protein domains. A nanobody does not automatically mean long action or simple therapy; the specific construct decides.

From camelid to active ingredient: how nanobodies are made

In a classic research workflow, an alpaca or llama is immunized with a harmless target protein. The immune system forms matching antibodies, and a blood sample is then enough. The genetic information of the VHH domains is obtained from the immune cells it contains and compiled into a library. In the lab, the candidates that bind the desired target most strongly and most specifically can then be selected from it.

Once the sequence is known, the animal does not have to keep supplying the eventual drug. The selected nanobodies are produced recombinantly, that is with the help of genetically programmed cells. For use in humans, they are often optimized further or humanized so that the human immune system is as unlikely as possible to recognize them as foreign.

The first approved nanobody: Caplacizumab

The step from an interesting lab technique to a real drug was achieved with Caplacizumab, known under the trade name Cablivi. The EU approved it in 2018, and the US FDA followed in 2019. The active ingredient is used for acquired thrombotic thrombocytopenic purpura, aTTP for short, a rare and life-threatening disease in which small blood clots form in vessels.

Caplacizumab binds von Willebrand factor and thereby prevents platelets from attaching in an uncontrolled way. The example is important because it shows that nanobodies are not just tools for experiments but can have a concrete clinical benefit as properly vetted medicines. In 2021, Envafolimab also came onto the market in China, a humanized VHH drug against PD-L1 for certain advanced tumors.

Llamas against flu and coronaviruses

Virus research is particularly illustrative. In 2018, researchers described in Science the multidomain antibody MD3606, which was assembled from four llama nanobodies. In the lab it neutralized 60 different influenza A and B viruses and protected mice in the models examined. The approach was thus not an approved universal flu vaccine, but it showed how several small binding domains can be combined into an exceptionally broad effect.

During the COVID-19 pandemic, the Belgian female llama Winter became known. A nanobody called VHH72, which came from her earlier immunization, recognized not only SARS-CoV-1 but, in adapted form, also the spike protein of SARS-CoV-2. Another llama, Wally, supplied particularly stable candidates that were even suitable experimentally for nebulization and thus for delivery directly into the airways. Here, too, the same holds: promising preclinical research is not yet approval as a drug.

A new antivenom from alpaca and llama nanobodies

A recent development step was published by an international team in Nature in 2025. After immunizing an alpaca and a llama with components from 18 snake venoms, the researchers selected eight nanobodies and combined them into a recombinant antivenom. In mouse models, the mixture protected against the lethal and tissue-damaging effects of 17 African elapids, including cobras and mambas.

The approach could one day complement classic antivenoms, which are mostly obtained from the plasma of immunized horses and, depending on the product, can trigger unwanted immune reactions. For now, though, these are preclinical results. Whether safety, dosage and efficacy convince in humans first has to be shown by clinical trials.

Not just nanobodies: the red blood cells are special, too

Antibodies are not the only peculiarity of camelid blood. Alpacas and llamas have elliptical instead of round red blood cells. The flat cells stay well mobile even under severe dehydration and tolerate an extraordinary increase in volume when water is taken up quickly. Together with their high number, this supports oxygen transport under the dry, oxygen-poor conditions of the Andes.

Nanobodies and oval erythrocytes have different jobs but tell the same biological story: camelids are adapted to extreme habitats, and some of these adaptations are proving scientifically valuable today far beyond the Andes.

Sources and context

Key foundations are the first description of heavy-chain antibodies by Hamers-Casterman and colleagues in Nature (1993), the 2022 review on nanobodies (PMCID: PMC9100996), the influenza study by Laursen and colleagues in Science (2018), the coronavirus work by Wrapp and colleagues in Cell (2020) and the antivenom study in Nature (2025, doi:10.1038/s41586-025-09661-0). Information on approvals comes from the FDA and the respective drug documentation. Results from cell culture and animal models are deliberately not presented in the article as therapy that is already available.