Discovery

Viruses change through mutation, which can lead to the emergence of variants. We are working at pace to keep up with the natural evolution of COVID-19 and study the effectiveness of currently available vaccines against variants of concern.

The natural evolution of SARS-CoV-2: How science responds to these challenges

Viruses, like SARS-CoV-2, constantly change through mutation, which can lead to the emergence of new variants. While mutations may lead the viruses to acquire variable mutations, some may lead to less severe disease or variations in viral functions, and others may lead to the virus being more easily transmitted or increase the severity of disease caused – these variants are termed variants of concern.

Studies have shown that currently available vaccines do provide some level of protection against new variants, but more studies will be required to fully understand their effectiveness. For us to fully understand the spread and evolution of new variants, continued surveillance is needed. This will also help us to prepare new strategies to overcome them. Experts agree that the current global roll out of the vaccines should not be delayed by the emergence of these new variants as the protection offered far outweighs the risks of a potential decrease in efficacy.

The origin of virus variants –is the SARS-CoV-2 virus unusual?

Virus variants arise from mutations in the viral genome and are a natural and expected occurrence.A mutation is a particular change in the genetic sequence of a virus compared with an accepted ‘original’ sequence.

Viruses which express such mutations are known as variants. Variants may simultaneously express numerous mutations, such as the 2020 SARS-CoV-2 variants arising in the UK and South Africa.2

SARS-CoV-2 variants have started spreading rapidly across the world, and many more are expected to develop and will need to be continually evaluated. Mutations are part of natural evolution and, although a mutation may change the severity of disease caused by the virus or how it is transmitted, usually only those that are advantageous to the virus will spread at higher frequencies.1

As of the beginning of March, there were three global variants of concern, which are named based on the country where they were first identified. The UK (B.1.1.7), South African (B.1.351) and Brazilian (P.1) variants have mutations which are thought to make them more transmissible. There are also early data to suggest that the UK variant is associated with a higher mortality risk than the wild-type SARS-CoV-2.

Next steps

Evidence suggests that the available COVID-19 vaccines may still produce a protective immune response against the new variants identified to date, however the level of efficacy, especially against severe disease, is yet to be defined.3 Tests can analyse the entirety of the immune response, including the B and T-cells response. Changes to vaccines can be made to target novel variants.

Implications of the emerging SARS-CoV-2 variants on the efficacy of the COVID-19 monoclonal antibodies

While vaccines train the immune system to fight a future infection, monoclonal antibodies mimic naturally developed antibodies to immediately neutralise SARS-CoV-2 infection.

The mutations in the emerging variants of SARS-CoV-2 may allow them to escape the action of these therapeutic interventions. that neutralise the virus in different non over-lapping neutralisation epitopes, the risk of the combination losing efficacy is considerably lower, as the virus would have to mutate in multiple locations to escape the action of both antibodies.4,5 As with the vaccines, continued surveillance of SARS-CoV-2 is the best approach to ensure their success and need for evolution into new and upgraded combinations.

Viral vectored technology

COVID-19 Vaccine AstraZeneca is a ‘viral vectored’ vaccine, whereby the genetic code of one of the coronavirus’ surface proteins, the spike protein, is inserted into a modified common cold virus -an adenovirus. The adenovirus has been genetically altered, removing the genetic code that would normally allow it to replicate, and in its place the coronavirus spike protein genetic code is inserted. The modified cold virus essentially acts as a ‘carrier’ of the spike protein genetic code.

After vaccination, the ‘surface spike protein’ is produced in the body’s cells, priming the immune system to attack the virus if it later infects the body.

‘Viral-vectored’ vaccines have been tested in clinical research for many years for Ebola, prostate cancer, MERS, malaria, tuberculosis, and influenza, and have consistently demonstrated to be effective with acceptable safety profiles.

Technology
 
References

1. Grubaugh ND, Petrone ME, Holmes EC. Why we shouldn’t worry when a virus mutates during disease outbreaks. Nat Microbiol. 2020;5:529-530

2. Davies NG, et al. Estimated transmissibility and severity of novel SARS-CoV-2 Variant of Concern 202012/01 in England [online ahead of print December 26, 2020] Available at: https://doi.org/10.1101/2020.12.24.20248822 (Accessed January 2021)

3. Wise J. Covid-19: New coronavirus variant is identified in UK. BMJ. 2020;371:m4857. Available at: https://doi.org/10.1136/bmj.m4857 (Accessed February 2021)

4. Cohen MS. Monoclonal Antibodies to Disrupt Progression of Early Covid-19 Infection. N Engl J Med. 2021;384:289–291

5. AstraZeneca. Phase III Double-blind, Placebo-controlled Study of AZD7442 for Post- Exposure Prophylaxis of COVID-19 in Adults (STORM CHASER). ClinicalTrials.gov website. Available at: https://clinicaltrials.gov/ct2/show/NCT04625972 (Accessed February 2021)

What a vaccine's "efficacy rate" actually means

 

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