Understanding How COVID-19 Virus Binds to Human Cells Offers ‘Key’ to Vaccine Development

As new variants of the SARS-CoV-2 virus necessitate the development of more vaccine options, research into the way the virus binds to human cells could offer a key to that development process.

Michael Cho, PhD, a professor of biomedical sciences at Iowa State University, is investigating ways to develop COVID-19 vaccines that specifically target the receptor-binding domain (RBD) of SARS-CoV-2, or the part of the virus that docks with the angiotensin converting enzyme 2 (ACE2). The process is what gives the virus access to the host’s cells, which leads to infection.

Cho and his team have developed an experimental vaccine that produced antibodies that attack the RBD of the virus. The RBD is the portion of the viral spike protein that binds to host cells to initiate infection, Cho said, and he likened the spike protein to a key. The RBD is the part of the key that actually enters the lock, he explained.

“The spike glycoprotein is the key that opens the lock, and the region of the key with all the peaks and valleys and grooves is the RBD,” Cho said in a press release. “If antibodies attack the RBD, then the key won’t work and the door will stay unlocked, preventing infection. We don’t really need to make antibodies against the entire spike protein, which is more difficult to make. We can just focus on the RBD portion.”

This approach differs from the 3 vaccines currently approved in the United States. The mRNA vaccines from Moderna and Pfizer/BioNTech work by teaching the immune system to make the entire spike protein that triggers an immune response. The Johnson & Johnson vaccine uses a modified version of a different virus to induce an immune response.

The research team conducted trials of the RBD subunit protein vaccine in mice and found that they induced a potent antibody response over the course of 3 injections. The study showed that 1 or 2 injections may be sufficient, depending on the adjuvant used. In the press release, Cho said he hopes to test the approach in human trials.

In addition to the benefits of its targeted approach, Cho said the RBD-targeting vaccine is relatively easy to produce and scale up because it requires only a small portion of the virus’s spike protein to manufacture. The vaccine can also be delivered multiple times, which could be necessary to develop immunity against the variants that will inevitably emerge.

Cho said the process of reaching herd immunity through vaccines will take time, which does allow for new variants to spread. This is especially true for populations in developing countries that have only had limited access to the currently available vaccines. Furthermore, as additional variants emerge, more vaccines will become necessary.

“Just because we have vaccines now, that doesn’t mean we won’t need more in 3 or 5 years, maybe even longer,” Cho said in the press release. “I don’t think our vaccine is too late to play a role.”

REFERENCE

The ‘key’ to new COVID-19 vaccine development [news release]. Iowa State University; May 10, 2021. https://www.news.iastate.edu/news/2021/05/10/rbdvaccine. Accessed May 19, 2021.