Jonathan Lovell and his team have discovered a technique that could help increase the effectiveness of vaccines against the novel coronavirus, the virus that causes COVID-19.
The team investigated the efficacy of designing vaccines that partially mimic the structure of the virus. 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.” In other words, 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.
Lovell’s 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, Lovell said.
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. According to Lovell, other vaccine adjuvant technology does not have the capacity to convert the RBD into particle-form.
The study was supported by the National Institutes of Health, and the Facility for Electron Microscopy Research (FEMR) at McGill University. FEMR is supported by the Canadian Foundation for Innovation, Quebec Government and McGill University.
Collaborators include Wei-Chiao Huang, Shiqi Zhou, Xuedan He and Moustafa T. Mabrouk, all from UB's Department of Biomedical Engineering; Kevin Chiem and Luis Martinez-Sobrido, both from Texas Biomedical Research Institute; Ruth H. Nissly, Ian M. Bird and Suresh V. Kuchipudi, all from the Animal Diagnostic Laboratory, Department of Veterinary and Biomedical Sciences at Pennsylvania State University; Mike Strauss and Joaquin Ortega from the Department of Anatomy and Cell Biology at McGill University; Suryaprakash Sambhara from the Immunology and Pathogenesis Branch of the U.S. Centers for Disease Control and Prevention; Elizabeth A. Wohlfert from the Department of Microbiology and Immunology at UB; and Bruce A. Davidson from the Department of Anesthesiology and the Department of Pathology and Anatomical Sciences at UB.
Lovell founded the Lovell Lab at UB in 2012. It is focused on developing novel nanomedicine approaches to meet unmet needs in treating and preventing disease. He is also a co-founder of POP Biotechnologies, Inc., a preclinical stage biotechnology company developing next-generation drug and vaccines products.