HONOURABLE MENTION

Gene/Viral Mutation

The simple definition of a mutation is a change in a DNA sequence. Mutations are from DNA copying mistakes made during cell division, being exposed to ionizing radiation. This project will look further in depth on gene mutation and how they occur
Aamna Ahmed
Grade 10

Problem

What is a viral mutation and are we able to stop them the same way as the original virus i.e Covid 19?

Method

In this project, I will be answering the question "What is a viral mutation, and are we able to stop them the same way as the original virus i.e Covid 19?'". I will be going into depth and explaining experiments that scientists have conducted to verify whether vaccines and other sources are able to stop Covid 19 and/or the mutated version. I will also be explaining each term in detail and drawing connections between viruses in the past (influenza) while carefully tying it back to covid 19 as it is an ongoing pandemic. The study I wrote in 'data' was collected at Emory University, collection and processing were performed under approval from the University Institutional Review Board. The trial was supervised by an independent safety monitoring committee. All participants provided written informed consent before enrollment. The trial was conducted under an Investigational New Drug application submitted to the Food and Drug Administration. The NIAID served as the trial sponsor and made all decisions regarding the study design and implementation.

Research

Research:

  • A gene mutation is a permanent alteration in the DNA sequence (genetic material) that makes up a gene, making it different from what is found in most people. 
  • It can be transmitted to the cell's or the virus’s descendants
  • Mutations occur in different sizes and they can affect anywhere from a single DNA building block to multiple genes and large sections of chromosomes

Gene Mutations can be classified in two ways

 

  • Hereditary mutations: This is inherited from a person’s ancestors and is present in every cell in the body. Mutations are present in the parent’s egg or sperm cells (germ cells), which is why they are also called germline mutations. When an egg and a sperm cell unite, the fertilized egg cell receives DNA from both parents. If this DNA contains a mutation, the child that grows from the fertilized egg will have the mutation in each of their cells. 

 

  • Acquired (or somatic) mutations: These occur at any time in a person’s life and are not present in every cell in the body. Environmental factors are the major cause for this, for example, ultraviolet radiation from the sun, or can occur if an error is made as DNA copies itself during cell division. Acquired mutations in somatic cells cannot be passed to the next generation.

 

Viruses are microscopic parasites, which are even much smaller than most bacteria that lack the capacity to survive and reproduce outside of a host body. When it attaches itself to a host body (depending on the specific proteins molecules on the cell) it uses the cell to create more virions. It destroys the cell and goes into more cells, repeating the process

Viral Mutations:

  • Mutations are changes to the sequence of an organism’s genetic code when there is a small error in the copying process 
  • Mutations can alter the structure of the viral envelope and choose which organs the virus attacks for example lungs or throat and if the genetic change causes the virus to spread, it prevails. It is proven that the higher the transmission rate the less likely any new mutations will add any improvement 
  • Viruses tend to mutate more rapidly than human cells do. This is because human cells can proofread the genome and also contain mechanisms that can repair a sequence in the genetic code if an error is found. Mutations can vary in severity from having zero consequence to completely changing a protein and its function.
  • Once a mutation occurs, if it changes the function of a resulting protein and as a result, a virus or organism is then fully altered.
  • Some of the reasons why Virus Mutations are increasing rapidly are due to natural selection, random genetic drift, or features of recent epidemiology. 
  • Viruses with RNA-based genomes (HIV) mutate faster than viruses with DNA-based genomes. 
  • The higher mutation rates in RNA viruses evolve faster and could evolve resistance to drugs more than DNA-based viruses
  • Average mutation rates in RNA based mutations are 100 times higher than DNA based mutations
  • RNA virus mutations are because of the lack of proofreading activity in polymers
  • SARS-CoV-2 is changing much more slowly as it spreads compared with HIV
  • In the issue of Cell, Korber et al. found that an amino acid change in the spike protein D614G quickly became common early during the pandemic and in April, viruses containing G614 are now spreading throughout the world. Korber saw the mutation appearing again and again in samples from people with COVID-19. It started in Europe but now has spread to multiple countries like Canada, America, Australia, etc. D614G is represented as a “more transmissible form of SARS-CoV-2”
  • clinical samples from G614 infections have a greater level of viral RNA present
  • Viruses that encode their genome in RNA, such as SARS-CoV-2, HIV, and influenza, pick up mutations quicker as they are copied inside their hosts. This is because enzymes that copy RNA are more likely to make errors as mentioned earlier
  • data suggest that coronaviruses transform more slowly than most other RNA viruses, most likely because of a ‘proofreading’ enzyme that corrects potential mistakes
  • When Scientists examined clinical data from 999 COVID-19 cases diagnosed in the United Kingdom, Korber et al. (2020) concluded that patients infected with viruses containing G614 had higher levels of virus RNA, however, there was no difference in hospitalization numbers. 
  • This variant also affected how t-cells function which has the job of killing virus-infected cells and help control the infection 
  • In the past and to this day, Flu or Influenza is a fast mutator and there is a new strain every year that results in yearly vaccines. 
  • When researchers were studying the novel coronavirus SARS-CoV-2 they concluded that the genomic mutation rate is lower than the flu. This is good as a lower mutation rate makes a vaccine effective for a longer period of time

 

  • We can use antibodies as a source to cure coronavirus
  • Antibodies are laboratory-made proteins that mimic the immune system’s ability to fight off harmful pathogens like viruses. They latch onto surfaces of the virus and inactivate or neutralize it. 
  • An advantage of this is that antibodies target the SARS-CoV-2 virus because they originate in the blood of people who have fully recovered from covid 19 which makes it more effective than other drugs
  • it can help those who are at high risk of severe disease because of weak immunity or a medical condition
  • On Wednesday, Eli Lilly said that the combination of two antibodies, bamlanivimab, and etesemivab, reduced hospitalizations and deaths in high-risk patients recently diagnosed with COVID-19 by 87 percent in trials
  •  The monoclonal antibody known as VIR-7831 had an 85 percent efficacy in reducing hospitalization or death from Covid-19 compared to a placebo.
  • However, this is only effective for the original strain of coronavirus
  • How are they made?
  • First, scientists attract the relevant antibodies from human blood. Then they replicate and replicate in large quantities. The majority of monoclonal antibodies are made in Chinese hamster ovary cells which are typically grown in around 10 to 15 days. The resulting antibody is then cleaned thoroughly and packaged.
  • Antibodies provide rapid protection against covid 19 infections as they enter the bloodstream straight away and offer immediate protection for a few weeks or months. This is short term protection however antibodies provide immediate protection meanwhile vaccines take weeks to be in effect

 

  • Vaccine:
  • Vaccines are chemicals that help the body develop antibodies
  • Biotech firm Moderna in Cambridge, Massachusetts, has invented an RNA-based vaccine and is expected to fight against the UK variant
  • Scientists found a way to swap vaccines’ old versions of the spike protein (original coronavirus) for an updated molecule that has the specific changes in amino-acid that antibody responses. But researchers are required to determine whether any such changes will change how an average person’s immune system reacts to the vaccine. Another idea scientists came up with is called the multivalent vaccine which consists of both new and old forms of the spike protein. However, these are still being studied
  • COVID-19 vaccines, including ones made by Moderna, Pfizer, and AstraZeneca, instruct cells to produce the virus’s spike protein (the immune system’s prime target for coronaviruses). Variants carry spike mutations that alter regions targeted by neutralizing antibodies.
  • Moderna and Pfizer/ BioNTech Vaccine: These vaccines are proven to protect against virus variants. However, it has shown a decrease in the antibody response from the South African Variant
  • A study showed that 16 people who received Pfizer vaccines came into contact with 10 mutations found in B117 were easily neutralized by antibodies in the samples, keeping vaccine efficiency high for this variant. This same vaccine was ⅔ less effective against the south African variant
  • Pfizer vaccine has effectively and successfully neutralized the coronavirus strain in Brazil and the UK variant as well. It has a “robust but lowers” effectiveness against the South Africa variant according to the letter to the New England Journal of Medicine
  • The AstraZeneca/oxford vaccine is said to have “minimal protection” against mild to moderate African variant cases. This means it will give protection from this variant however there is a chance one might contract it. It is only 10 percent effective against it. Studies show it is 74.6 percent effective against the UK variant
  • The Novavax vaccine is 95.6 percent effective overall and 85.6 percent effective against B117 and 60 percent effective against the African Variant.
  • Biotech firm Novavax released data from clinical trials showing that its experimental vaccine, designed for the original virus, was about 85% effective against a variant identified in the United Kingdom but 50% less effective against African Variant.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Data

 

Viral sequences: Bar chart showing sequence counts for 31 countries or regions.

Mutation worry grows for vaccines | Hindustan TimesWhat Are the New COVID-19 Variants, and How Can We Track Them? - IEEE  Spectrum

However, the above vaccine effectiveness chart does not specify mutated virus and their effect on vaccine efficiency for coronavirus (different strains). Suthar and his colleagues experimented with 20 patients with an acute infection, 20 recovered individuals, and 14 healthy vaccines against a panel of SARS-CoV-2 variants. The people who were immunized between the ages of 18 and 55 years had received two injections of Moderna's mRNA-1273 vaccine and after 14 days received a second dose. The SARS-CCoV-2 variants consisted of D614G and B117 variants. These researchers found out that the antibodies were effective at neutralizing all variants they tested. The team stated "these results show that neutralizing antibody titers following natural infection or vaccination is effective against the UK variant and viral streams containing single point mutation at positions 501 and 614 within the spike protein"

This data proves that the Moderna vaccine is effective against the new strain of coronavirus, also known as the UK variant.

Conclusion

The original question that I asked was diving into what viral mutation was and if we were able to stop them the same way as the original virus i.e Covid 19. I was able to fully conclude that a mutation is a change to the sequence of an organism’s genetic code when there is an error in the copying process. Viruses attach themselves to a host body and use it to create more virions. This then destroys the cell and goes into more cells, repeating the cycle. During this process, it is possible to make an error as viruses are not able to proofread the genome the same way human cells can. RNA-based genomes mutate faster than DNA-based genomes. SARS-CoV-2 is an RNA genome and picks up mutations faster. The mutated version of this virus had an even greater number of RNA. In addition to this, scientists have found ways to cure coronavirus using vaccines and antibodies. Antibodies are developed by the body’s immune system to fight pathogens like viruses while vaccines are chemicals injected into the body to help it develop antibodies. However, we have concluded that due to the multiple different strains of the virus, these strategies will not work the same way. Many of the vaccines were less effective, especially for the African variant. Research also proves that the UK variant is affected by most of the vaccines. I have concluded that the original vaccine can be used on the variants however its effect will not be the same as the original.

 

 

Citations

The University of North Carolina at Chapel Hill. (2020, November 12). Common SARS-CoV-2 mutation may make COVID-19 more susceptible to a vaccine: Mutation is not expected to interfere with the effectiveness of vaccines under development. ScienceDaily. Retrieved March 17, 2021 from www.sciencedaily.com/releases/2020/11/201112144040.htm

Nature News (8 September 2020). The coronavirus is mutating - does it matter?. Retrieved March 15 from https://www.nature.com/articles/d41586-020-02544-6

Genome BC, Virus evolution: what do viral mutations mean for vaccine efficacy? Retrieved on March 11 from https://www.genomebc.ca/blog/virus-evolution-what-do-viral-mutations-mean-for-vaccine-efficacy

Business Insider, (November 20, 2020) 3 coronavirus vaccines so far seem to prevent COVID-19. Here's how their efficacy compares to vaccines for flu, measles, and more. Retrieved on March 2 from https://www.businessinsider.com/how-pfizer-coronavirus-vaccine-compares-other-vaccines-2020-11

PLOS Biology, (November 3, 2020) Why are RNA virus mutation rates so damn high? Retrieved on March 4 from https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000003

Wired (December 24, 2020) Here's a Plan to Stop the Coronavirus From Mutating Retrieved on March 15 from https://www.wired.com/story/heres-a-plan-to-stop-the-coronavirus-from-mutating/

Jove (not specified) Viral Mutations | Protocol retrieved on March 12 from https://www.jove.com/science-education/10827/viral-mutations

Judy Stone, January 26, 2021, 12 most common questions asked about covid mutation and vaccines retrieved on March 14 from https://www.forbes.com/sites/judystone/2021/01/16/12-most-common-questions-about-covid-mutations-and-vaccines/?sh=2be7e35f386b

The Conversation, Feb 2, 2021, Coronavirus variants, viral mutation and COVID-19 vaccines: The science you need to understand retrieved on March 15 from https://theconversation.com/coronavirus-variants-viral-mutation-and-covid-19-vaccines-the-science-you-need-to-understand-153771

Kai Kup, January 15, New coronavirus variants could cause more reinfections, require updated vaccines, retrieved on March 10 from https://www.sciencemag.org/news/2021/01/new-coronavirus-variants-could-cause-more-reinfections-require-updated-vaccines

Julia Ried, June 15, 2020, Covid 19 will mutate and what that means for vaccines, retrieved on March 7 from https://www.healthline.com/health-news/what-to-know-about-mutation-and-covid-19#What-this-means-for-a-vaccine

JAMA Patient Page, March 1, 2021, The Johnson & Johnson Vaccine for COVID-19 retrieved on March 15 from https://jamanetwork.com/journals/jama/fullarticle/2777172

https://www.scientificamerican.com/article/the-most-worrying-mutations-in-five-emerging-coronavirus-variants/

Sarah Rearon, January 29, 2021, The Most Worrying Mutations in Five Emerging Coronavirus Variants retrieved on March 10 from https://www.ctvnews.ca/health/coronavirus/new-coronavirus-mutation-raises-vaccine-questions-1.5264776

Academic Press, 12 Feb 2016 Viral Evolution: It Is All About Mutations retrieved on March 12 2021, from https://www.sciencedirect.com/science/article/pii/B9780128009642000173

Acknowledgement

I would like to thank my school Joane Cardinal-Schubert for giving me the opportunity to do this project and participating in the science fair.  Also to Ms. Sung who has provided me with encouragement and support throughout the process. She guided me in formulating my general thoughts into more focused ideas and helped me in developing the question I wanted to ask. I really appreciate all her hard work. Lastly, I would like to thank all members and volunteers in the CYSF for making this year’s science fair possible.