The “key” to vaccine development depends on virus binding to human cells


New variants of the SARS-CoV-2 virus will most likely require the development of more vaccine options in the coming years, and a biomedical scientist at Iowa State University believes the “key” to this development is how whose virus binds to humans. cells.

Michael Cho, professor of biomedical sciences at Iowa State, is studying how to develop COVID-19 vaccines that target the SARS-CoV-2 receptor binding domain, or the part of the virus that synchronizes with the host cell receptor, angiotensin-converting enzyme 2 (ACE2). This anchoring process allows the virus to gain access to the host’s cells, resulting in infection.

Cho was the lead author of a study recently published in the peer-reviewed scientific journal Frontiers in immunology detailing a vaccine’s ability to induce antibodies in mice that target the receptor binding domain of the virus. The patent-pending vaccine approach is available for license from the Iowa State University Research Foundation. Cho will make a virtual presentation on the potential of BioConnect Iowa’s vaccine and immunotherapy meeting approach on Wednesday.

The antibodies produced by the experimental vaccine attack the receptor binding domain, or RBD, of the virus. RBD is the part of the viral spike protein that binds to host cells to trigger infection. Cho likens the spike protein to a key, and the RBD is the part of the key that actually goes into the lock.

The peak glycoprotein is the key that unlocks the lock, and the key region with all of the peaks, valleys, and grooves is the RBD. If antibodies attack the RBD, the key will not work and the door will remain locked, preventing infection. We don’t really need to make antibodies against all of the spike protein, which is more difficult to make. We can just focus on the RBD part. “

Michael Cho, Professor, Biomedical Sciences, Iowa State University

This approach differs from the three vaccines currently available in the United States to ward off COVID-19. The mRNA vaccines produced by Pfizer and Moderna work by providing a set of instructions that teach the immune system how to make all of the spike protein that triggers an immune response. The Johnson & Johnson vaccine is known as a viral vector vaccine which uses a modified version of a different virus.

Cho and his colleagues conducted trials of the RBD subunit protein vaccine in mice and were able to induce a potent antibody response in rodents over three injections. The study showed that one or two injections are sufficient, depending on the adjuvant used. Cho said he would like to test the approach in human trials.

Easy to produce, scalable

The vaccine targeting RBD has certain advantages over vaccines currently licensed in the United States. Cho said the experimental vaccine is relatively easy to produce and scale because it only requires a small portion of the virus’s spike protein to make it. The RBD vaccine can also be given multiple times, which might be necessary to develop immunity against several viral variants that will inevitably emerge.

Cho said the process to achieve herd immunity to COVID-19 through vaccines will take time, which will allow new variants of the virus to spread. This is especially true for people in developing countries who have so far had limited access to currently available vaccines. And as more and more variants emerge, the likelihood that additional vaccines will become necessary increases, he said.

“Just because we have vaccines now, doesn’t mean that we won’t need more in three or five years, maybe even more,” he said. “I don’t think our vaccine is too late to play a role.”


Journal reference:

Niu, L., et al. (2021) A structural landscape of neutralizing antibodies against the SARS-CoV-2 receptor binding domain. Frontiers in immunology.

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