Modular system builds effective vaccines

The University of Oxford researchers who developed the mi3 nanoparticle.

There are two ways to make vaccines: use a virus or bacterium and kill or modify it; or produce a single part of the virus or bacterium, a so-called antigen, which trains the immune system to recognize the whole pathogen. The first approach carries a small risk of negative side effects; the second is less effective. Theodora Bruun and her colleagues at the University of Oxford have developed a nanoparticle that promises to be both safe and effective (ACS Nano10.1021/acsnano.8b02805).

Their particles display 60 copies of the antigen. This high concentration of antigens in one place makes it easier for the immune system to recognize them, compared with recognizing 60 individual antigens. While such particles are not new, previous versions were not soluble or stable enough and had a low production yield.

Stable particles from volcanoes

The new nanoparticle that the Oxford University team developed is based on a protein from the bacterium Thermotoga maritima, which was found in hot springs near a volcano. In fact, it is the only bacterium known to live at such high temperatures.

The mi3 nanoparticle (purple) can be decorated with any antigen using the SpyCatcher-SpyTag system. (Courtesy: ACS Nano10.1021/acsnano.8b02805. © 2018 ACS)

The researchers computationally optimized a thermostable protein from this bacterium to form a dodecahedron. The nanoparticles contained 60 copies of this optimized protein, called mi3. Bruun and co-workers showed that these particles are highly stable and survive temperatures of up to 75 °C, freezing and freeze-drying. The production yield was 10-fold higher than for a previously used particle.

Every one of the 60 copies of mi3 per particle is connected with a “SpyCatcher” molecule, which can covalently bind a “SpyTag” molecule, simply through mixing the two components. By attaching antigens to the SpyTag, a variety of vaccines can be made based on the mi3 particle.

Such a modular system has many advantages. “Developing a modular and robust nanoscaffold … could contribute to major challenges in human and animal health, including vaccines to rapidly evolving pathogens (e.g. HIV, malaria) or zoonotic outbreaks (e.g. Ebola virus, Rift Valley fever),”  the authors explain. The particle core could be stockpiled and combined with relevant antigens to enable a rapid response to outbreaks.

But does it work?

To test whether the new particle is suitable for vaccination, the researchers attached a malaria antigen using the SpyCatcher-SpyTag docking system. Compared with individual antigens, the antigen-decorated particle resulted in a more robust immune response, producing more antibodies (one of the two systems of specific immune defences in the body; the other being killer cells). The particle not only produced more antibodies than the individual antigens, but the antibodies produced were more effective, binding the antigen tighter.

So far, it seems that the new nanoparticle developed by Bruun and her team may prove a promising new tool to develop vaccines.