COVID-19 Mutations: How Variants Will Affect Vaccine Development

Since the beginning of the COVID-19 pandemic, scientists were aware of the potential for variants to mutate over time—this is a natural phenomenon for most viruses. Some of these variants pop up and die out, while others linger. There have been multiple variants of the SARS-CoV-2 virus, each with unique genetic changes. One feature to note on the SARS-CoV-2 virus is the spike protein located on its surface. This lock and key spike protein enables the virus to gain entry into host cells. Scientists have been analyzing this spike protein on variants and trying to determine if mutations are altering the infectious nature of the disease as well as the lethality. Currently, multiple COVID-19 variants are circulating. Llet’s take a look at some of these new strains and what they mean.

China

Of the many mutations on this strain, it is the D614G that is getting a lot of attention. Discovered in March 2020, the amino acid in the spike protein at position 614 is altered from aspartic acid to glycine. This mutation causes a change in the spike protein, the protein that uses ACE2 receptor to enable viral entry. This is the mutation thought to enhance the variant’s infectious ability.¹

United Kingdom (UK)

The UK presented one variant in September 2020—B.1.1.7—that has shown a number of mutations. Of these mutations eight B.1.1.7 mutations are located in the spike glycoprotein, including N501Y in the receptor binding domain, deletion 69_70, and P681H in the furin cleavage site. All of these mutations could plausibly influence ACE2 binding and viral replication. The mutations indicate it allows the virus to spread faster, increasing its infectious ability. There is no evidence that shows this variant is more deadly than the original virus. Since September, there have been confirmed cases of this variant in the United States and Canada, as well as other countries around the world.²

South Africa

Detected in October, this variant, E484K, shares some similarities with the UK variant. For instance, they share the N501Y mutation. Again, this variant increases the virus's ability to infect faster and more easily, but there is no evidence that it is more deadly than the original. E484K has posed some concern for vaccine efficacy as the new variant may be able to escape some of the antibodies produced by the vaccine. It has been noted that E484K has multiple mutations in their spike, or S, proteins.³

USA

Researchers at The Ohio State University Wexner Medical Center and College of Medicine have found a new variant of SARS-Cov-2 as well. The mutation is identical to the U.K. strain, however, probably evolved from a virus strain in the United States. The researchers also report the evolution of another U.S. strain that acquired three other gene mutations not previously seen together in SARS-CoV2.

Vaccine Efficacy Going Forward

Pfizer and the University of Texas Medical Branch have researched whether the Pfizer/BioNTech vaccine can handle the new variants that pose a potential escape route for vaccine efficacy. In their study, researchers used blood samples from 20 participants of the ongoing Phase 3 trial that had already received both doses of the vaccine. The antibodies in the patients’ blood were successfully able to neutralize SARS-CoV-2 with the N501Y mutation with the same efficacy demonstrated against the original virus. With more research to be done, researchers are at the early stages of addressing the vaccine's effectiveness against these variants but the initial data is promising, suggesting the vaccine should be just as capable of neutralization.

Antibody Drug Enhancement (ADE) has been a primary consideration for safety since the beginning of the COVID-19 vaccine’s development rush. ADE occurs when titers of one antibody dip below a certain limit, enabling other serotypes of the virus to seek the other antibodies and lead them more efficiently to immune cells.

This has been demonstrated in other viruses, such as dengue fever. Recently, researchers have been able to address ADE by utilizing a specific type of antibody. In the case of dengue fever, there are four serotypes of the virus, and building an antibody for one serotype can lead to antibody drug enhancement (ADE) to the others. Scientists using the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science User Facility located at the DOE's Argonne National Laboratory, have reported the application of a specific antibody to ensure efficacy on all four serotypes.

The antibody, called 2B7, blocks the NS1 protein, preventing it from attaching itself to cells and inhibiting transfection. The antibody attacks the protein directly, not just the virus particle itself, enabling 2B7 to be effective against all four strains of the dengue virus.⁴

In the event that ADE develops in terms of COVID-19, researchers will need to employ strategies in attacking the virus particle. It is important to note that due to the new nature of the virus, researchers have not confirmed whether ADE will be an issue, but further research and investigation will continue as the virus evolves.

Conclusion

The nature of the viruses guarantees there will be more variants over time. Evidence thus far suggests variants are potentially more virulent, but none have demonstrated an increase in mortality. Typically, as viruses grow within a population time works in favor of shaping more infectious, less deadly variants. However, the nature of COVID-19 is relatively new to human beings and scientific professionals need to continuously monitor these mutations for epidemiological significance.

References:

1. Zhang L, Jackson CB, Mou H, et al. The D614G mutation in the SARS-CoV-2 spike protein reduces S1 shedding and increases infectivity. Preprint. bioRxiv. 2020;2020.06.12.148726. Published 2020 Jun 12. doi:10.1101/2020.06.12.148726
2. Bram Vrancken, Simon Dellicour, Davey M Smith, Antoine Chaillon bioRxiv 2021.01.12.426373; doi: https://doi.org/10.1101/2021.01.12.426373
3. Tegally H, Wilkinson E, Giovanetti M, et al. Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa. medRxiv 2020.
4. Biering, Scott B., Akey, David L, et al. Structural basis for antibody inhibition of flavivirus NS1-triggered endothelial dysfunction. Science 08, Jan 2021: Vol 371 DCI: 10.1126/science abc0476

About the Author:

Chris Cicinelli is the Associate Editor for Labcompare and American Laboratory.