Technique Could Help COVID-19 Vaccine Effectiveness

In early December, the developers of several vaccines for the SARS-CoV-2 coronavirus announced good results in large trials. Notably, a vaccine made by Pfizer with German biotech firm BioNTech became the first immunization to be approved for emergency use.

But back in summer 2020, Lovell and his team discovered a technique that could help increase the effectiveness for a next-generation vaccine against the novel coronavirus, the virus that causes COVID-19.

Lovell, an associate professor of biomedical engineering, is the principal investigator on the research, titled “SARS-CoV-2 RBD Neutralizing Antibody Induction is Enhanced by Particulate Vaccination,” which was featured on the inside front cover of the Dec. 17, 2020, issue of Advanced Materials.

According to Lovell, 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.” That is, he says, antibodies against this part of the virus have the potential to neutralize the virus.

It would be “appealing if a vaccine could induce high-levels of antibodies against the RBD,” Lovell says. “One way to achieve this goal is to use the RBD protein itself as an antigen, that is, the component of the vaccine that the immune response will be directed against.”

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 Lovell Lab is focused on developing novel nanomedicine approaches to meet unmet needs in treating and preventing disease. His 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, says Lovell.

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, Lovell says.

“We think these results provide evidence to the vaccine-development community that the RBD antigen benefits a lot from being in particle format,” Lovell explains. “This could help inform future vaccine design that targets this specific antigen. Our rapid platform enabled our study to be the first peer-reviewed report about the efficacy and potential of nanoparticle-based RBD vaccines.”

The promising approach of CoPoP RBD particles has also gained interest from industry. The technology, which has been licensed to POP Biotechnologies Inc. — a UB spinoff company co-founded by Lovell — may soon see its first human in the not-distant future.

POP Biotechnologies Inc. is collaborating with EuBiologics Co. of South Korea to sterile manufacture a CoPoP/RBD vaccine fit for human trials.

The study was supported by the U.S. 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.

Co-authors from the University at Buffalo are:

• Wei-Chiao Huang, PhD, a postdoctoral associate in the Department of Biomedical Engineering
• Shiqi Zhou, Xuedan He and Moustafa T. Mabrouk, students in the Department of Biomedical Engineering
• Elizabeth A. Wohlfert, PhD, assistant professor in the Department of Microbiology and Immunology
• Bruce A. Davidson, PhD, research associate professor in the Department of Anesthesiology

Co-authors from Texas Biomedical Research Institute are:

• Kevin Chiem, a fourth-year doctoral student
• Luis Martinez-Sobrido, PhD, professor in the Disease Intervention and Prevention program

Co-authors from the Animal Diagnostic Laboratory, Department of Veterinary and Biomedical Sciences at Pennsylvania State University are:

• Ruth H. Nissly, research technologist
• Ian M. Bird, doctoral candidate
• Suresh V. Kuchipudi, PhD, clinical professor and head of microbiology section; associate director of the Animal Diagnostic Laboratory

Co-authors from the Department of Anatomy and Cell Biology at McGill University are: 

• Mike Strauss, DPhil, assistant professor of anatomy and cell biology
• Joaquin Ortega, PhD, professor of anatomy and cell biology

Suryaprakash Sambhara, PhD, is a co-author from the Immunology and Pathogenesis Branch of the U.S. Centers for Disease Control and Prevention.

Although the paper was featured in the Dec. 17, 2020, issue of Advanced Materials, it was first published online on Oct. 28, 2020.