An experimental COVID-19 vaccine containing gold nanoparticles and coronavirus RNA successfully triggered an immune response in mice, laying the groundwork for further testing and demonstrating the promise of nanotechnology in vaccine development.

A team of Mexican researchers at the Autonomous University of San Luis Potosí published the results March 2 in a paper in Nanomedicine: Nanotechnology, Biology and Medicine. They say their nanovaccine prototype — though in very early stages of development and not yet tested in humans — could create complete immunity to COVID-19, unlike currently administered vaccines.

The application of nanotechnology in vaccines, known as nanovaccinology, is a growing field that uses particles thousands of times smaller than the width of a human hair to enhance the immune responses provoked in the body. These nanoparticles have been applied to transport antibody-triggering antigens or make them more potent. 

Many forms of nanovaccines are still under development, but some have already been commercialized, such as a hepatitis B vaccine in 1986 and a human papillomarivus vaccine in 2006, which made use of virus-like particles that have viral structures but are non-infectious.

Gold nanoparticles are a popular building block for nanovaccines because they are inert in the body and are easily absorbed by certain immune cells. They have previously been used as carriers or enhancers in nanovaccine research, and have also attracted medical attention for their antimicrobial and anti-inflammatory properties.

The researchers aimed to use gold nanoparticles as vessels to transport RNA from the novel coronavirus into the immune cells of mice, which would create antibodies in response. The coronavirus' "spike" protein is crucial for its entry into cells, so the researchers attached numerous copies of a segment, or peptide, of the spike-protein gene to the gold, so that they emanated outward in all directions. A compound called thiol-PEG-amine was used to glue them together.

Mice were administered either the coronavirus peptide alone or the nanoparticle-peptide conjugate, and the immune response produced was found to be four times greater in the gold-infused solution. Its effect was as strong as the peptide paired with Freund's adjuvant, an antigen solution that can strengthen the immune response to vaccines but is not safe for human use due to side effects.

"Our group has been working in resolving stability issues of AuNP [gold nanoparticles] when we want to use them as vaccines," said Omar Gonzàlez-Ortega, an author of the paper and a professor of chemical sciences at the Autonomous University of San Luis Potosí. "We have been able to successfully address many of these issues such that we can have an effective vaccine."

Additional testing is needed for the nanovaccine before it may be applied in humans, said Sergio Rosales-Mendoza, also a chemical sciences professor at the university and another author of the paper. He said the next steps include tests in large animals, such as sheep or goats, to determine dosage and safety. 

The researchers said it is important for developing countries such as Mexico to have a domestic and cheap COVID-19 vaccine, which the gold nanovaccine could possibly provide because of its inexpensive components. Mexico has authorized five vaccines, all produced in other countries: the U.K.'s AstraZeneca-Oxford, the U.S. and Germany's Pfizer-BioNTech, Russia's Sputnik V and China's CanSino and Sinopharm.

"The candidate vaccine proposed in our work does not require the production and purification of complex recombinant proteins since it only uses synthetic peptides that are cheaper and easily available," Gonzàlez-Ortega and Rosales-Mendoza said. "At least in Mexico, our findings contribute to establish that metallic nanoparticles could render cheap vaccines and justify the evaluations in larger animal models."

Just under four vaccine doses per 100 people have been administered in Mexico, which is higher than most Latin American countries but much lower than the U.S.'s 34.6 doses per 100 people. As of Sunday, Mexico had experienced 2.2 million COVID-19 cases and 198,000 related deaths.

The two professors, who have long researched nanovaccines and wrote a book on the topic, said their approach to vaccines may have another advantage: complete prevention of COVID-19. Sterilizing immunity, as it is known, stops viruses from replicating within the body and also stops them from spreading to others.

COVID-19 vaccines currently in use are unlikely to provide sterilizing immunity, the researchers said, but their vaccine candidate might open up new approaches to achieving it. Sterilizing immunity is not necessary to curb the pandemic, though vaccines that provide the benefit would be even more effective at stopping its spread.

The study, "Synthesis and immunogenicity assessment of a gold nanoparticle conjugate for the delivery of a peptide from SARS-CoV-2," published March 2 in Nanomedicine: Nanotechnology, Biology and Medicine, was authored by Susan Farfán-Castro, Mariano García-Soto, Mauricio Comas-García, Jaime Arévalo-Villalobos, Gabriela Palestino, Omar González-Ortega and Sergio Rosales-Mendoza, Autonomous University of San Luis Potosí.