BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: #COVID (Page 3 of 3)

Robert Malone: The Man Behind the Ideas for the COVID Vaccine

When you think of the COVID-19 vaccine, the first things that might come to mind are the companies that facilitate it (such as Pfizer & Moderna), if it is safe or not, or even that it is a new type of mRNA vaccine that is unfamiliar to many. However, people tend to overlook and not give any thought towards who made this all possible, and that person is Robert Malone.

Robert Malone, born in 1959, started his medical career at University of California Davis, and later got his MD from Northwestern University. After Malone’s traditional education at both an undergraduate and graduate level, he conducted research at the Salk Institute for Biological Studies.

Salk Institute (19)Salk Institute for Biological Studies

During his time at the Salk Institute, Robert Malone performed a “landmark experiment.” In this experiment, Malone mixed strands of mRNA with droplets of fat (lipids). Human cells reacted with this mRNA lipid mix and began producing proteins from it. Robert Malone had some foresight and realized that this discovery has some potential in the medicinal world. He decided to jot down some notes, stating that if cells could create proteins from mRNA delivered to them that it might be possible to “treat RNA as a drug (written January 11, 1988).”

These revelations from Robert Malone had a huge contribution towards the mRNA COVID-19 vaccines.

COVID-19 Vaccine vial and syringe - US Census

After seeing all of this information on how Robert Malone made scientific contributions towards the COVID-19 vaccine, it is important to show how it works. Since we know (as seen in Malone’s experiments) that mRNA mixed with lipids that enter a human cell can lead to the production of proteins, scientists just had to tweak the mRNA until it could create pieces of “spike protein.” These pieces of spike proteins would have to match the shape of the spike proteins found on the surface of the COVID-19 virus. This required an impressive feat of biomedical engineering, but it was done.

Robert Malone’s work did not just contribute to the first strand of COVID-19 discovered, but his work applied towards different variants as well.

Corona virus Covid-19 BW

The idea of spike proteins and how spike proteins can be counteracted through an mRNA vaccine applies to all different variants of COVID-19. As seen through activities and lessons learned in our Bio class, different variants of COVID-19 just have pieces of the protein structure changed, which leads to a changed shape of their spike proteins. This leads to existing vaccines being less effective as the original vaccine was meant for a specific spike protein shape, not the shapes of the new variants. This means that mRNA vaccines are still very much effective towards different variants of COVID-19, but they would have to be modified mRNA vaccines.

Despite all of this, Robert Malone’s research’s applications might not stop at the COVID-19 vaccine. The COVID-19 vaccine was able to show us the power of mRNA vaccines, so it is not unreasonable to be expecting more mRNA vaccines in the future.

Mutation in the Nation

We constantly think of SARS-CoV-2, the virus that causes COVID-19, as a single virus, one enemy that we all need to work together to fight against. However, the reality of the situation is the SARS-CoV-2, like many other viruses, is constantly mutating. Throughout the last year, over 100,000 SARS-CoV-2 genomes have been studied by scientists around the globe. And while when we hear the word mutation, we imagine a major change to how an organism functions, a mutation is just a change in the genome. The changes normally change little to nothing about how the actual virus functions. While the changes are happening all the time since the virus is always replicating, two viruses from anywhere in the world normally only differ by 10 letters in the genome. This means that the virus we called SARS-CoV-2 is not actually one species, but is a quasi-species of several different genetic variants of the original Wuhan-1 genome.

The most notable mutation that has occurred in SARS-CoV-2 swapped a single amino acid in the SARS-CoV-2 spike protein. This caused SARS-CoV-2 to become significantly more infective, but not more severe. It has caused the R0 of the virus, the number of people an infected person will spread to, to go up. This value is a key number in determining how many people will be infected during an outbreak, and what measures must be taken to mitigate the spread. This mutation is now found in 80% of SARS-CoV-2 genomes, making it the most common mutation in every infection.

Glycoproteins are proteins that have an oligosaccharide chain connect to them. They serve a number of purposes in a wide variety of organisms, one of the main ones being the ability to identify cells of the same organism.  The spike protein is a glycoprotein that is found on the phospholipid bilayer of SARS-CoV-2 and it is the main tool utilized in infecting the body. The spike protein is used to bind to host cells, so the bilayers of the virus fuse with the cell, injecting the virus’s genetic material into the cell. This is why a mutation that makes the spike protein more efficient in binding to host cells can be so detrimental to stopping the virus.

In my opinion, I find mutations to be fascinating and terrifying. The idea that the change of one letter in the sequence of 30,000 letters in the SARS-CoV-2 genome can have a drastic effect on how the virus works is awfully daunting. However, SARS-CoV-2 is mutating fairly slowly in comparison to other viruses, and with vaccines rolling out, these mutations start to seem much less scary by the day.

 

CRAZY NEW COVID-19 Mutation Makes Virus Weaker Against Antibodies

As revealed in a fascinating article that details a study conducted by the University of North Carolina at Chapel Hill, a mutated form of the virus has been discovered to be much more susceptible to antibodies produced by antibody drugs. This means that it is more easily disabled by antibodies produced by drugs such as the new vaccine. However, this may not all be good news as this new strain, called D614G, is also much more transmissible. D614G originated in Europe and has quickly become the most prevalent form of the virus. According to professor of epidemiology at UNC Ralph Baric, “The virus outcompetes and outgrows the ancestral strain by about 10-fold and replicates extremely efficiently in primary nasal epithelial cells, which are a potentially important site for person-to-person transmission.” These nasal epithelial cells act as a physical barrier against any pathogens attempting to enter the body and play a significant part in the control of the innate and acquired immune response. As we learned in biology, one method of innate immune response that our bodies have is mucous that traps pathogens. The nasal epithelial cells contain cilia that act to push the mucous and the pathogen contained inside out of the body. This means that if this new virus reproduces exceptionally well within the nasal epithelial cells, then it is extremely transmissible through any expulsion of mucous by either sneezing or coughing. It is also far more capable of bypassing the barrier of the mucous and entering the body. These epithelial cells also help the innate immune system by producing various cytokines. If a virus manages to make it past the barrier defenses, the epithelial cells will secrete cytokines. These cytokines will attract a type of cell called a neutrophil that digests pathogens. This means that these nasal epithelial cells are vital to the innate immune response and having a virus strain reproduce so effectively inside of them is extremely worrying.

The researchers believe that D614G is so effective at reproducing because it increases the virus’ ability to enter cells. The D614G mutation opens a flap on the tip of one of the spikes on the side of the virus which allows it to infect cells more effectively. However, this mutation also creates a weakness in the virus. When the flap is open, it becomes much easier for antibodies to bind to the spike proteins, preventing the virus from attacking additional cells.

Two researchers from the University of Wisconsin contributed to this study by experimenting with hamsters. To test the airborne aspect of this mutation, the hamsters were placed into different cages and groups so they could not touch and inoculated with either the original strain or D614G. By day two, in the group exposed to the mutation, six out of the eight hamsters were infected with D614G. In the group of hamsters exposed to the original virus, no additional hamsters were infected by day 2. This shows that this D614G is extremely effective at being transmitted airborne. However, the mutation had the same symptoms and effects as the original virus meaning it is not more severe. The researchers have also noted that these results may not be the same in human studies. I think that this study is equal parts of good and bad news. I am glad that the most prevalent form of the virus is much easier to deal with, but it is quite terrifying that it could mutate to be so much more contagious. How do you feel about this new development? Let me know in the comments. 

Testing!

When you hear the word “COVID -19 testing” what comes to mind? I have this vivid image of a cotton swab being pushed up my nose. But what exactly is testing? Why is it so important? And what are the types of testing available for our use?

We’ve all heard that testing is important but why? To summarize a supplementary article, COVID testing “leads to quick identification of cases, quick treatment for those people and immediate isolation to prevent spread” (Dr. Eduardo Sanchez). When discovered at an early stage, COVID will be less a threat to a person because doctors can plan accordingly while COVID is still less severe. Even when a person discovers they have COVID not as early as hoped, testing helps to identify anyone who came into contact with infected people so they too can be quickly treated. Contact tracing would not be possible without testing because a person would never know if they are spreading the virus. The only way to be better safe than sorry is to get tested. Someone may show symptoms that are COVID-like but there is still a chance that it could be a common cold, or allergies. It is important to confirm COVID suspicion.

Now that we know why testing is important, what kind of testing is out there? What I found in this FDA article is what I like to call a family of tests; there are numerous different tests to take.

To start things off, let’s talk about Diagnostic testing. Diagnostic testing shows if you have an active coronavirus infection. As of right now, there are two types of diagnostic tests: molecular and antigen tests. Molecular tests detect the virus’ genetic material in a sample from the patient’s nose or throat. This is where test results will take longer because they are sent to labs. From there, the lab essentially converts the virus’s RNA into DNA, and then make millions of copies of the DNA to be processed in a machine. The test is “positive” for infection with SARS-CoV-2, the virus that causes COVID-19. Examples of molecular diagnostic tests include nucleic acid amplification test (NAAT), RT-PCR test, and the LAMP test. Next, there is Antigen diagnostic testing. Antigen tests provide results from an active coronavirus infection faster than molecular tests. The downside to these tests are that they have a higher chance of missing an active infection. Sometimes an antigen test may come back negative, but a doctor might still order a molecular test to confirm.

Different from Diagnostic Tests, there are Antibody (different from Antigen) tests. These tests looks for antibodies that are made by your immune system in response to a threat, such as a specific virus. As we learned in biology class, antibodies can help fight infections. These tests are taken by finger stick or blood draw, and the results are quick. The antibody test only shows if you’ve been infected by coronavirus in the past. But do antibodies help diagnose COVID-19? As we learned in class about the Immune System, our body can fight pathogens, bacteria, and viruses that we have been previously exposed to. While this was a popular belief earlier on in the year, sadly, researchers do not know if the presence of antibodies means that you are immune to COVID-19 in the future. It is possible to contract COVID-19 for a second time, therefore adaptive immunity does not apply.

The most common testing that I knew of before researching was rapid testing. Rapid testing can be both a molecular or antigen diagnostic; a doctor uses a mucus sample from the nose or throat. The test can also be taken at home only by prescription of a doctor. The results are available in minutes. There is also saliva testing where a person can spit into a tube; this also keeps the doctor or worker safer from the potentially infected person.

Testing is the best way to keep yourself and those around you safe. While testing is still not 100% accurate, there is currently no better way to confirm if someone has COVID-19 unless he/she get tested. With this pandemic, we can never be too safe!

 

 

 

 

 

LION: The King Of The COVID Vaccines

As the SARS-CoV-2 virus (also known as COVID-19) continues to rage across the world killing millions, more time, effort, and money is being put into researching the best vaccines to help bring the world back to a state of normalcy.  One such vaccine is being developed at the University of Washington using replicating RNA is called LION (Lipid InOrganic Nanoparticle). In its animal trials in July, the vaccine already found some success inducing “coronavirus-neutralizing antibodies” in mice young and old which has given researchers a lot of hope for the future of the vaccine.

 

One might wonder, why do we need a vaccine at all? Vaccines are used to expose your body to small doses of a virus or in this case by mRNA, which teaches your body to produce the antibodies needed to fight the virus and makes memory cells. The next time you are exposed to the virus, your body will be able to produce the necessary antibodies to a much larger degree, much quicker, for longer so you will be protected from becoming sick.

One of the lead researchers on LION, Professor Deborah Fuller of the University of Washington School of Medicine qualified the goals of a successful COVID-19 vaccine saying it, “will ideally induce protective immunity after only a single immunization, avoid immune responses that could exacerbate virus-induced pathology, be amenable to rapid and cost-effective scale-up and manufacturing, and be capable of inducing immunity in all populations including the elderly who typically respond poorly to vaccines.” This is quite a lot to accomplish but LION lends itself very well to these goals, conquering most of the problems a typical DNA vaccine would have. DNA vaccines work by coding for the antigens which are then exposed to the immune system to create memory cells so the body can treat the virus later. The downsides of a DNA vaccine is sometimes those antigens fail to create an immune response or can even cause the cell to become cancerous when the DNA joins the host cells DNA, disrupting it. There is far less risk with RNA vaccines which occupy the cytoplasm and only interact with ribosomes.

Shown above us a basic drawing of what SARS-CoV-2 virus looks like.

LION is a replicating RNA vaccine, but how does replicating RNA work? RNA codes for spike proteins and ribosomes in the body make the necessary proteins. Replicating RNA allows for more spike proteins and ribosomes to be coded at a greater rate, which produces a greater number of proteins continuously while triggering “a virus-sensing stress response that encourages other immune activation.” For the vaccine the RNA replicates proteins that tell the body to reject the SARS-CoV-2 and attack them “with antibodies and T cells”  which stop the protein spikes on the virus from interfering with the cell. The development of B cells, which remember how to make the antibodies to fight the virus when infected again, as well as T cells is especially critical for the vaccine as they can develop immunity to the SARS-CoV-2 antigens. What makes the LION vaccine special is the nanoparticle it is named after which “enhances the vaccine’s ability to provoke the desired immune reaction, and also its stability.” This makes it more valuable than other vaccines of the same kind as it can achieve effective results with a longer shelf life. It can also be mixed simply using a two vial method as the mRNA component is made separately from the main vaccine formulation. For all these reasons, the scientists are optimistic as the vaccine goes into the next stages of testing that this vaccine could help provide a long term solution to the COVID-19 pandemic.

As COVID-19 vaccines start becoming available to essential workers in the coming weeks and my father prepares to take one, it can be quite unnerving to think about all the potential negative side effects of the vaccine. These vaccines have been developed without the typical ten years of testing, so knowing more about the research behind the vaccines serves as a comfort me and many others. Our future is in these vaccines and research so knowing which we should invest our time and money in is always a good idea.

ARE WE DOOMED? Maybe not

     Well, this year has been a ride. Starting off with a potential WWIII, continuing with the tragic loss of hall of fame athlete Kobe Bryant, 2020 has been one roller coaster of a year. But the most bizarre of it all was the COVID-19 pandemic. The pandemic swept the nation way back in March and it still has its grasp on us today. At the time it started, there was very little information on this virus. But now, due to our vast intricate technologies, we were able to find out lots of information on this virus. But, specifically, I want to talk about life after contracting the virus. See, normally when you have a virus and successfully heal from it, you develop antibodies so you will not get this type of virus again. The case is a bit different for COVID-19, or it might be the same. Read to find out!

     This topic is very interesting because there have been more than 10 million people who have acquired the virus. The people that have successfully recovered from the virus want to know the main question: Will I be able to get this virus again? The answer isn’t so simple. Early on the data provided to us gave us hope that the immunity to this virus was possible, but numerous cases also suggest that this immunity to the virus is brief (on a larger scale). Nothing is definite as of now, there is more research to be done, but for now we remain hopeful. 

 

So why do we say the immunity to the virus is brief?

     We know there is hope because there is proof that people who have contracted COVID-19 produce antibodies that protect our immune system, but this production of antibodies lasts maybe 3 to 4 months based on the data provided. The length of time still remains unclear. 

 

So how does this actually work?

     Researchers from Massachusetts General Hospital tested three types of antibodies in blood samples: immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin B (IgB). Immunoglobulin is a large Y-shaped protein used in the immune system to detect foreign invaders in the blood such as viruses. These proteins bind to these foreign invaders in order to fight them off. We learned from our unit with proteins that antibodies are a form of proteins that can influence the life of a molecule/virus. The most important of all the immunoglobulins stated above is IgG. The reason is because IgG has the potential to sustain immunity in the body. This is because when all three of these antibodies were found in the blood after being infected by COVID-19, IgA and IgB were obliterated by the spike protein found in COVID-19. But, IgG lasted in the stream for up to four months! Now, the researchers could not test IgG for that long, but the four months that they could observe showed that these IgG antibodies do persist to beat the virus! A more long term study is definitely needed. This study is also confirmed by another research group from the University of Toronto. This group also showed how IgA and IgB levels dropped rapidly about 12 days after infection while IgG levels remained steady. 

 

So can you get COVID more than once?

     Although it is very rare, there have been some cases where people contracted the virus more than once. But, there is no evidence that suggests that immunity is or is not possible. All in all, evidence shows that immunity after acquiring the virus is generally protective and the persistence of the IgG antibody provides hope for immunity to the virus. – Ghohesion

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