Nanoparticle-based vaccine offers new approach to COVID-19 immunity

Physics

Jae Jung, from Cleveland Clinic’s Global Center for Pathogen Research & Human Health, and collaborators have developed a promising new COVID-19 vaccine candidate. (Courtesy: Cleveland Clinic)

As the international effort to vaccinate the population against COVID-19 gathers pace, the demand for vaccine doses that can be used in all countries and climates is enormous. Researchers from Cleveland Clinic and Chungbuk National University have described a new vaccine candidate that triggers an immune response using antigens attached to nanoparticles, potentially bypassing the need for cold storage during delivery. They report their findings in mBio.

All vaccines approved to date cause an immune response against the same part of the SARS-CoV-2 virus: the receptor binding domain (RBD) of the spike protein. However, they employ different mechanisms to bring this about – from using inactivated viruses to cause RBD production to delivering genetic instructions directly into cells. This new candidate provides an alternative approach – using inert nanoparticles to carry the RBD and display it to the immune system.

Direct delivery

Delivering the RBD protein directly, rather than causing the cell to produce it, seems an appealing option for vaccination. However, the body’s immune defences won’t respond to such a small molecule. Attaching multiple RBD units to a larger nanoparticle overcomes this challenge and makes them visible to the immune system. The nanoparticles used in this study are built from ferritin – a naturally produced protein existing in most organisms that can self-assemble into a useful nanoparticle structure.

The researchers tested the vaccine candidate in ferrets – which are susceptible to the same respiratory infections as humans. They saw that after three injections with this vaccine, the vaccinated ferrets had high levels of antibodies against SARS-CoV-2 in their bloodstreams. Ferrets treated with the vaccine and then exposed to the virus did not experience symptoms and cleared the virus from their system far quicker than unvaccinated ferrets.

The researchers were even able to show how vaccinated ferrets avoided lung damage caused by the infection. They note that combining intramuscular injection with introducing the vaccine through the nose – where SARS-CoV-2 commonly enters the body – produced an even stronger protective effect.

A hot topic

One of the biggest challenges in vaccinating the world’s population is getting the vaccine efficiently to every place it is needed. The vaccines in current use all need consistent cold storage, and in some cases ultracold storage, to remain effective. By being built from a nanoparticle structure that is naturally very thermostable, this new candidate may not need such conditions.

“This protein is an attractive biomaterial for vaccine and drug delivery for many reasons, including that it does not require strict temperature control,” says study author Jae Jung.

“This would dramatically ease shipping and storage constraints, which are challenges we’re currently experiencing in national distribution efforts. It would also be beneficial for distribution to developing countries,” adds co-first author Dokyun Kim. The authors note that this stability needs to be more rigorously verified, but were it to remain true, this could be one tool to help reduce global inequities in vaccine availability.

Any vaccine candidate still has many stages to progress through before it is approved for widespread use in humans, but the data so far for this approach are promising. If the vaccine comes to fruition, it will add a different type of weapon to the already diverse arsenal available to combat the continuing COVID-19 pandemic.

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