Reassuring .//
By Lea Wilson Contributing writer
Nov 29, 2021
For the delta, delta plus, and kappa variants of COVID-19, the difference between transmissibility, the ability to evade vaccine neutralization, and the structure of their spike glycoproteins is no longer a mystery. A study published Nov. 9 in Science by professor David Veesler’s lab in the department of biochemistry gave new insights into the coronavirus.
The information from this study will help determine why some coronavirus variants are more widespread than others and will aid in the development of more effective vaccines.
A key part of this study was being able to determine the structures of the spike proteins. The spike glycoprotein of the coronavirus is at the surface of the coronavirus and helps the virus enter human cells and infect them. It includes receptor-binding domains (RBDs), parts of the virus that send signals that allow it to attach to cells, and the N-terminal domain, which helps the virus find places where it can attach to the cell.
Most vaccines target these parts of the virus, but this also happens to be where significant mutations occur.
“In particular, we found a pretty dramatic change in structure in the N-terminal domain of the delta spike, and of the 11 neutralizing antibodies that we had tested, 10 of them just didn’t really bind well anymore,” Matthew McCallum, a postdoctoral fellow at the Veesler Lab and one of the lead authors of the study, said. “The one antibody that did bind reasonably well, we structurally characterized where it was binding and it bound to a somewhat unique site, and that particular site could be interesting and worth investigating.”
Identifying the structure of the spike proteins of variants of the coronavirus is important in helping scientists determine where mutations in this structure occur and in developing a vaccine that targets parts of the structure that stay the same for multiple variants.
According to the study, although the delta variant isn’t as effective at evading vaccines as the delta plus and kappa variants are, it has become globally prominent due to attributes that enhance transmissibility. Veesler’s findings suggest one of these attributes is a mutation that allows the virus to divide the parts of its DNA that play a role in how effectively the virus transmits itself and causes sickness.
Based on how widespread the delta variant is, the Veesler Lab finding that this variant isn’t effective at evading the vaccine is important in suggesting that a variant’s ability to spread among a population is more important than its ability to be stronger than a vaccine.
As more studies are published that determine which part of the coronavirus can be targeted to neutralize it, the more effective vaccines can become. Currently, scientists are looking at the S309 antibody to create a universal coronavirus vaccine.
“The S309 antibody binds to a site on the RBD, which is on the spike glycoprotein and that particular site doesn’t mutate between the variants, apparently, which makes S309 … extremely useful because you can use it on people who have any of the variants,” McCallum said.
Knowing which antibody targets sites on the coronavirus helps researchers determine which antibodies to include in vaccines, making them more effective. Since the S309 antibody targets a site that doesn’t mutate between different variants, it could potentially be used in a vaccine that is able to protect against many variants.
Studies on the coronavirus are continuously being released, bringing forth new information and influencing further studies. Scientists working together and sharing information is an important part of effective, timely research.
“A lot of people in our lab were involved in this, and many, many people who I am so grateful for and several collaborators,” McCallum said. “We did this pretty quick, actually, we knew we had to be quick because this was so important and everything related to [the coronavirus] has to be really quick.”
The authors of the study included scientists from the UW department of biochemistry, UW Division of Allergy and Infectious Diseases, UW Center for Emerging and Re-emerging Infectious Diseases, Vir Biotechnology in San Francisco, and Humabs BioMed SA in Bellinzona, Switzerland.
Reach contributing writer Lea Wilson atnews@dailyuw.com. Twitter: @leaswilson
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