CNSI experts examine COVID-19 vaccine efforts

Nanotechnology advances enable coronavirus vaccine design, offer potential to overcome challenges


by Wayne Lewis

Nanoparticle construction to deliver RNA vaccines: One of the problems with delivering RNA to the translational machinery of the cell is the risk that the RNA itself will degrade before it reaches its destination. To prevent this, vaccine makers employ cationic lipid nanoparticles, which were originally developed for cancer immunotherapy and other vaccines. Condensed into solid lipid nanoparticles, messenger RNA can be delivered to and taken up by targeted cells (Illustration by Marc Roseboro/CNSI).

As COVID-19 inoculation efforts continue to ramp up in the U.S. and around the world, two leaders at the California NanoSystems Institute at UCLA recently took stock of the unprecedented success of vaccine design efforts, as well as the challenges ahead.

The Pfizer and Moderna vaccines currently being administered shattered the previous record for how quickly a vaccine could be developed and deployed, which had been four years. This progress was driven in part by nanotechnology, which involves interactions on a scale of billionths of a meter. The paper’s authors predict that as scientists address questions for the future about achieving durable immunity and keeping coronavirus variants from evading that immunity, nanotechnology will likewise play an important role.

The review article, published in ACS Nano, was written by immunologist Dr. André Nel, a UCLA distinguished professor of medicine, director of research at CNSI, and director of the University of California’s Center for Environmental Implications of Nanotechnology, and microbiologist Jeff F. Miller, UCLA’s Fred Kavli Professor of NanoSystems Sciences, the director of CNSI and a professor of microbiology, immunology and molecular Genetics.

In a comprehensive look at vaccine candidates and the mechanisms by which they engage the immune system, Nel and Miller lay out three broad approaches to vaccine development that all benefit from nanometer-scale delivery technologies:


  • At the heart of vaccines such as the approved ones from Pfizer and Moderna is messenger RNA, which provides genetic instructions for producing proteins that trigger an immune response. This mRNA is packaged in lipid nanoparticles that both protect it and deliver it to lymph nodes, where certain immune cells are trained to respond to the coronavirus. Lipid nanoparticles are specifically designed to facilitate uptake and delivery of their mRNA cargo to the cytoplasm of immune cells, where antigen expression occurs.
  • Subunit vaccines elicit an immune response using whole coronavirus proteins or pieces of them, encapsulated within nanoparticles or engineered to self-assemble into nanoparticles. The Novavax candidate currently in late-stage clinical trials is an example of a subunit vaccine.
  • Epitope vaccines stimulate immunity with parts of the coronavirus where antibodies attach, fragments that can also be delivered with nanoparticles.

The very newness of COVID-19 limits our ability to forecast how long vaccine-borne immunity will last, although early signs are promising. The authors cover some of the key factors that could influence the durability of the anti-coronavirus immune response, and describe several strategies for nanocarrier design that could enhance antibody production or improve cooperation among different types of immune cells.

Some concern remains that as the coronavirus mutates, new variants will bypass immunity promoted by vaccines. One potential safeguard described in the review involves updating nano-enabled vaccines to target structures seen in coronavirus variants; the mRNA Pfizer and Moderna vaccines, for instance, are rapidly modifiable.  In addition, both vaccines induce T cells in addition to antibodies which contribute to protection.

With an eye toward the future, Nel and Miller also explore how the success of COVID-19 vaccine design may provide advantages for creating vaccines to prevent other diseases such as the flu and HIV/AIDS. They note that delivering vaccine updates for the coronavirus could become as much a fact of life as the need to update computer software; at the same time, nanotechnology-based and -adjacent advances, including advanced computation, may yield more-effective COVID-19 vaccines in the years to come.