Designing COVID-19 Vaccine That Partially Mimics Structure Of SARS-CoV-2 Virus Could Increase Its Effectiveness

One of the proteins on the virus - located on the characteristic COVID spike has a component called the receptor-binding domain, or RBD, which is its “Achilles heel.” Antibodies against this part of the virus have the potential to neutralize the virus. The team hypothesized that by converting the RBD into a nanoparticle (similar in size to the virus itself) instead of letting it remain in its natural form as a small protein, it would generate higher levels of neutralizing antibodies and its ability to generate an immune response would increase.

The team had previously developed a technology that makes it easy to convert small, purified proteins into particles through the use of liposomes, or small nanoparticles formed from naturally-occurring fatty components. In the new study, the researchers included within the liposomes a special lipid called cobalt-porphyrin-phospholipid, or CoPoP. That special lipid enables the RBD protein to rapidly bind to the liposomes, forming more nanoparticles that generate an immune response. The team observed that when the RBD was converted into nanoparticles, it maintained its correct, three-dimensional shape and the particles were stable in incubation conditions similar to those in the human body. When laboratory mice and rabbits were immunized with the RBD particles, high antibody levels were induced. Compared to other materials that are combined with the RBD to enhance the immune response, only the approach with particles containing CoPoP gave strong responses. Other vaccine adjuvant technology does not have the capacity to convert the RBD into particle-form, according to the researchers.

“We think these results provide evidence to the vaccine-development community that the RBD antigen benefits a lot from being in particle format. This could help inform future vaccine design that targets this specific antigen,” said Jonathan F. Lovell, PhD, associate professor in the Department of Biomedical Engineering at UB, the primary investigator on the research.

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