BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: SARS-CoV-2

Could protein-based vaccines change the course of the pandemic?

Current mRNA vaccines provide sufficient protection against new SARS-CoV-2 variants, including Omicron, particularly for those who have received boosters. However, due to high manufacturing costs and the requirement for ultra-cold refrigeration, these vaccines are limited in low and middle-income countries. Protein-based vaccines have the potential to be much less expensive to manufacture on a large scale than mRNA vaccines and may not require ultra-cold storage. Protein vaccines would aid in delivering more vaccines to areas of the world where vaccination rates are currently extremely low, such as Africa to the lack of vaccines.

A research program in Cellular and Molecular Medicine (PCMM) is presenting a new strategy to build a better vaccine to directly target the antigen cells with a protein-based vaccine. This is not the first time we hear about protein vaccines; they have been around for decades now to protect others from hepatitis, shingles, and other infections. The protein-based vaccine will deliver proteins while also stimulating the immune system to respond to the vaccine more aggressively directed to the person’s cells. The protein-based vaccine will also enable a more efficient T cell response and high antibody production across variants while causing fewer side effects than other Covid-19 shots.

T Regulatory Cells

T regulatory cells (red) interact with antigen-presenting cells (blue) in a microscope image.

In connection to cell-to-cell communication, protein-based vaccines rely on the T cells to target the infected cells. The T-helper cells are able to divide and create two different types of cells. The T killer cell kills infected cells with the virus. Others, called T memory cells, stimulate the production of antibodies to prevent reinfection. In addition, the primary immune response will expose some of the antigens but the secondary immune response facilitates a faster, stronger, and longer response to the antigen produced due to the memory cells. 

Could Protein-based vaccines be used instead of the mRNA-based vaccines that are currently approved to protect against Covid-19?

 

 

 

 

SARS-CoV-2 and Our Evolving Immune Systems

A scientific study analyzed in a recent article by Monique Brouillette brings hope with the emergence of possibly more infectious COVID-19 variants. The study looks at the blood of people who are vaccinated, and people who recently have had COVID-19, to learn more about the cells in our immune system. Studying and seeing these cells create their own way to counteract mutations could mean the evolution of our immune systems in response to the variants. So the study poses the question: Along with our cells ability to respond to the initial SARS-CoV-2 virus invasion, do our bodies adapt so that those same cells can recognize the new variants?

An Immunologist at the Rockefeller University, Michel Nussenzweig, conducted a study along with his colleagues by testing the blood of individuals both one month and seven months after they had COVID-19. The scientists noticed that individuals had lower levels of antibodies, and equal or higher levels of memory B cells, seven months after having COVID-19 than one month after. This was expected as the virus had been fully cleared by the seven month mark, and memory B cells were created in response to the initial invasion of SARS-CoV-2.

Memory B cells are created by the humoral response. This is when macrophages or dendritic cells recognize a forign antigen (in this case SARS-CoV-2), and stay in the body near its lymph nodes with the ability to recognize the virus.

Memory B cell response

If someone were to get infected for a second time, these memory B cells would activate to quickly produce antibodies and block the virus. This is called the secondary immune response (pictured on the right).

The scientists then did another test in the study. They tested reserve B cells and antibodies someone produced in response to SARS-CoV-2 against a version of SARS-CoV-2 they created to be more like a new variant. The replica new variant virus was made to be more like the new variants by having a mutation in the spike protein, which is the part of the virus that binds to our cells. When they tested this, they saw that some reserve B cells produced antibodies that went and attached to the mutated spike proteins, showing that the reserve B cells and antibodies from SARS-CoV-2 were able to adapt and recognize a different or mutated version of SARS-CoV-2.

New COVID19 mutant (SARS-CoV-2 VOC-20201-01)

Example of SARS-CoV-2 Mutation

The SARS-CoV-2 variants have many similar elements to the original SARS-CoV-2, but also contain mutations in their spike proteins and receptor binding domains (for the most part), which allow them to usually go undetected by our bodies. This is why those who are vaccinated or have SARS-CoV-2 antibodies are not fully immune to the variants.  

Most recently, Nussenzweig and his team conducted the same experiment again, but with new and improved viruses that more closely resemble the COVID-19 variants. One of the replica variants is of B.1.351, which contains mutations K417N, E484K, and N501Y, was tested against cloned six month old (previously exposed to SARS-CoV-2) B cells. Although it has not yet been reviewed and confirmed, this test did show that some of the antibodies produced by these B cells had the ability to recognize and attach to these mutated variants engineered to be very similar to the viruses of the Covid variants. 

What these scientists discovered with SARS-CoV-2 is a process called somatic hypermutation. This is when the immune system adapts to recognize and attack forign mutations or viruses it has not seen before when they have previously fought off a virus with some similar elements. The occurrence of this process with SARS-CoV-2 gives us hope that after getting the vaccine or having had COVID-19, our bodies will have a better defense against the new variants, which will, hopefully, in turn, lessen the fear and stress surrounding the emergence of new SARS-CoV-2 variants.  

 

 

 

Changing Course: How Scientists Can Update Vaccines With Emerging Variants

SARS-CoV-2 , the virus which causes COVID-19, is changing rapidly, which in turn warrants changes to the vaccines created to slow its spread. This virus is mutating fast, with a new mutation establishing about every 11 days. These mutations may not be different enough to cause an immediate difference, but each and every person who catches SARS-CoV-2 opens more possibilities for mutations.

Spike omicron mutations top

Omicron Mutation Spike Protein

The most recent large variant to be identified was B.1.1.529 Omicron originating in South Africa. The Omicron variant has more than half the amount of mutations as the Delta variant, raising concern among health officials, who fear that the virus may differ just enough from the original for vaccines to be less effective. This fear stems from the idea that the vaccine-created antibodies will no longer be able to recognize the mutated virus’ spike proteins, resulting in an ineffective vaccine.

The current mRNA SARS-CoV-2 vaccines work in a fascinating way. Scientists utilize harmless lab-grown mRNA that contain coded instructions on how to create the SARS-CoV-2 spike protein, and place that technology into a vaccine.

Then, once the mRNA vaccine is injected into the patient, the patient’s cells will create the identical spike proteins, prompting an immune response. As we have learned in AP Bio, the adaptive immune system would eventually churn out antibodies tailored to the spike protein, so any future SARS-CoV-2 virus that enters the body will be neutralized and destroyed, even before it has the chance to infect someone.

Solo-Viral Vector-vaccine-27

SARS-CoV-2 Vaccine Vial

Because of this technology, scientists are readily able to create an updated version of the SARS-CoV-2 vaccine within a matter of days, for distribution in around three months. How do they “update” the vaccine? First, the Omicron spike protein is sequenced into their nitrogen bases (A, T, G, and C’s). Once that is complete, scientists use this sequence to create a DNA template. They then mix in enzymes which build an mRNA copy of the DNA template through a process known as transcription.

This process unfolds in a matter of days… so why does it take three months? Creating the physical mRNA for the vaccine takes only three days, but then the vaccine makers need to produce enough mRNA for doses, which would be used the next six weeks in pre-clinical testing on human cells. Once pre-clinical testing is complete and proves the vaccine works as expected, then the manufacturing of the vaccine can begin. The vaccine wouldn’t be released just yet — the next five weeks would be clinical trials and testing, and after that, the updated vaccine can begin rolling out to the public.

Even though SARS-CoV-2 is evolving faster than vaccines can keep up with, past technology was no where near as quick as today’s. In my eyes, being able to produce an updated vaccine in a matter of months is nonetheless a scientific feat. Comment what you feel was a gigantic scientific leap during this pandemic below!

An Antidepressant Is The Next “Weapon” Against COVID-19

Is the COVID-19 vaccine the only way to lower death rates and hospitalization rates? While more individuals are becoming vaccinated against COVID-19, researchers have looked at how a low-cost antidepressant prescription could potentially tackle the virus. Fluvoxamine (Luvox), an antidepressant medication, has the capacity to reduce hospitalization and morality rates after patients receive COVID-19 within a few days. Although fluvoxamine is licensed by the FDA for the treatment of obsessive-compulsive disorder (OCD) and other disorders such as depression, it is not approved for the treatment of COVID-19. In a study, conducted in Brazil, 1,500 newly diagnosed COVID-19 patients were assessed. 741 of the participants received a 100 mg pill of fluvoxamine twice a day for 10 days and the remaining 756 participants received a placebo twice a day. 16 percent of those who took the placebo twice a day got ill enough to necessitate a lengthy hospital stay compared to 11 percent of those who took fluvoxamine. Researchers discovered that participants who took at least 80% of the fluvoxamine administered to them had a two-thirds lower chance of hospitalization! Furthermore, there was only one fatality among individuals that took fluvoxamine, compared to 12 fatalities in the placebo group. According to The Lancet Global Health, this research has shown that the drug has reduced morality rates by roughly 91 percent. The antidepressant drug can be easily prescribed by doctors for COVID-19 using their clinical judgement.

Diagnostics-10-00453-g001

When the COVID-19 virus enters the body through the eyes, nose, or mouth and travels to the lungs, the immune system strives to protect itself from the invading pathogens by producing antibodies that, on occasion, eliminate invading infections. If the invading pathogen is unfamiliar to the body, B-memory cells will be unable to detect it, and B-plasma cells (antibody secreting cells) will be unable to manufacture antibodies, allowing the virus to enter the cell and flourish in the body.

Fluvoxamine

Fluvoxamine is a 2-aminoethyl oxime ether of aralkylketones. The antidepressant medication, if taken promptly after receiving COVID-19, may be an additional method of minimizing viral transmission and accompanying medical concerns. Fluvoxamine is easy to get and inexpensive to manufacture, particularly as a generic drug. COVID-19 treatments, in general, serve as both a cure for severe sickness and a treatment for the beginning of illness. Fluvoxamine, as an SSRI (selective serotonin reuptake inhibitor), attaches to a cell’s receptor that governs cellular stress response and the generation of cytokines, proteins that alert the body of a problem and lead to extreme inflammation. Nevertheless, fluvoxamine has been shown to minimize inflammation. When people get COVID-19, it’s theorized that the damaged cells produce a slew of cytokines that generate inflammation in the lungs, making it difficult to breathe. Patients would be able to breathe better and require fewer hospitalizations if fluvoxamine was taken to help decrease inflammation.

Fimmu-11-01648-g002

Who knew that an antidepressant that inhibits the serotonin reuptake pump at the presynaptic neuronal membrane might reduce inflammation and allow you to breathe? Because fluvoxamine works by boosting serotonin levels between nerve cells in the brain, it is impressive that the medicine might be used for purposes other than treating depression or OCD. The lingering question is whether someone with COVID-19 who has been taking these antidepressants for a previous disorder has an edge.

Are Genes Inherited from Neanderthals Protecting People Against COVID-19?

Neanderthals, from roughly 40,000 years ago, have had an impact on protecting people, that contain a specific haplotype on chromosome 12, from having severe symptoms due to the Sars-COV-2 virus. Researchers conducted a study that showed a ~22% decrease in severe illness connected to a gene inherited from Neanderthals.   

Neanderthals evolved in western Eurasia -the largest continental area consisting of Europe and Asia- about half a million years ago, living mostly separated from early modern humans in Africa. Neanderthals likely developed certain genes allowing them to fight off infectious diseases during the time of their existence. Due to natural selection, which is when animals with the most favorable traits for survival will survive to reproduce and pass on their genes, these neanderthals were able to evolve and pass on the favorable gene allowing modern humans today to fight off Sars-Cov-2. Through natural selection, the haplotype, on chromosome 12, linked to protection against certain viruses has been passed on. This specific haplotype has helped people during the current pandemic to stay out of the hoHuman male karyotpe high resolution - Chromosome 12spital. 

This study discovered that this specific haplotype on chromosome 12 contains three helpful genes: OAS1, OAS2, and OAS3. These genes encode for a specific enzyme called oligoadenylate synthetase. As we learned in AP Biology, enzymes are created by free ribosomes in the cytosol; the ribosomes manufacture proteins(a chain of amino acids), such as enzymes for cellular reactions. The oligoadenylate chain triggers ribonuclease L. The ribonuclease L, also known as RNase L, is only activated when a viral infection enters the body; it breaks down the viral RNA molecules, leading to autophagy. This enzyme breaks down the viral Sars-Cov-2 RNA and slows/stops the spread of the virus in the body. 

Many people have been trying to find ways to move forward from this pandemic and return to our previous form of normal life. Scientists may be able to use this information about this specific haplotype on chromosome 12 with gene editing technologies, such as CRISPR, to help individuals slow and later stop the spread of COVID-19. Research like this may be one way to be able to return to a normal life-style and keep people out of hospitals from COVID-19. As we continue on in AP Biology this year, I look forward to learning about the idea of genes and gene editing as I will have more knowledge to touch back on this research study. Do you think that this is a possible solution to the COVID-19 pandemic?

 

 

Comparing Saliva Tests to Nasopharyngeal Swabs

Although many college campuses have closed within the past couple of weeks, for the few months they were in session, the general public was introduced to a new procedure for COVID-19 testing: Saliva tests. There are multiple reasons why a saliva test would be more ideal for campuses to use, and it’s not just because the nasopharyngeal swab testing is extremely uncomfortable.

A nasopharyngeal swab is basically a biological term for the COVID-19 test that goes all the way up your nose. News-Medical actually came out with an article going through the testing procedure, and how the SARS-CoV-2 is detected. The purpose of the swab test is to reach the nasopharynx, which is where nonpathogenic and pathogenic bacteria and viruses lie. It’s also used to test the flu and pneumonia. In fact, UC Davis published that they have just come up with a rapid test that could detect both the flu and COVID-19 in one nasopharyngeal test. This makes it the most convenient method, but it’s more expensive; making this harder to upscale for mass testing). It also requires more supplies, and puts health care workers in close contact with infected individuals. Saliva tests would be a lower cost, but there was uncertainty in its accuracy. The Scientist highlights three main experiments that help better our understanding of saliva testing.

The first experiment was led by Yale epidemiologist, Anne Wylie. Wylie and her colleagues tested the accuracy of swab testing using 70 suspected COVID-19 patients admitted to the Yale-New Haven Hospital. They found that saliva samples contained more copies of the SARS-CoV-2 than swabs. The group concluded by saying that they see potential in the saliva swab; however, this was only tested in one controlled area, and the patients at this point were showing symptoms.

The second experiment, led by Mathieu Natcher, took place throughout the French Guiana. There were 776 participants ranging from (wealthier) villages, forests, and more poor neighborhoods. Natcher discovered that the SARS-CoV-2 virus was still present within saliva for a long period of time, despite climbing temperatures, which makes this idea for situations where testing needs to happen in areas where temperature can’t be regulated. The one downside noticed during this experiment was that saliva testing was less sensitive than nasopharyngeal swabs, which means that it can be harder to pick up the bacteria, if there is less in their system. Therefore, saliva testing may not always be as efficient for asymptomatic carriers or people who just became infected.

Pharmacologist at the University of South Carolina helped develop the school’s saliva test, and reported her findings after school came back in session. She noticed that although saliva may be less sensitive, the repetition of testing these students makes it more possible to catch the infection shortly after it comes. She also ran an experiment on two students living together: one of which had a confirmed COVID-19 diagnosis, and the other was at risk. Both students got tested daily using the nasopharyngeal and saliva swabs for the two weeks. She found that the amount of the virus detected in both tests for the positive patient were the same, leading her to conclude that saliva and nasopharyngeal tests both have the same sensitivity. Banister also explained that not the lower sensitivity coming from the saliva test in comparison to the nasopharyngeal test could be due to the fact that saliva turns over quickly in the mouth, while the nasal cavity and lungs hold the virus for longer. Banister also said because of this saliva tests might be a more accurate depiction of who is actually infectious, because the virus stays in the lungs even after the patient is no longer infectious.

We have come a long way since this article was initially posted, and saliva tests have been released to more of the public for a longer period of time. It is interesting to see how these preliminary tests played a role in whether or not to further release saliva tests.

So we beat SARS and MERS… Why haven’t we beat COVID-19?

Many people, especially those who were alive during the SARS and MERS outbreak, may be wondering why we haven’t beat the Coronavirus yet if we beat the SARS and MERS outbreaks, two very similar viruses to COVID-19 or Sars-CoV2. This is a question many people have been facing everyday as the Coronavirus disease has caused a shift in the entire globe’s day to day life unlike SARS and MERS. 

SARS, MERS, and COVID-19 are all part of the coronavirus family. “Coronaviruses are a large family of enveloped RNA viruses” that can be found in a variety of bat and bird species. While this makes the three viruses similar, they all have specific differences causing unique results in terms of outbreaks and how the specific viruses have spread. What is so powerful or different about the coronavirus causing COVID? 

First of all, let’s talk about how viruses hijack our bodies. Viruses are microscopic parasites, much smaller than bacteria, that contain key elements that make up all living things such as nucleic acids and DNA or RNA, but are unable to replicate and access this information encoded in their nucleic acids, meaning they cannot self replicate. In order to reproduce, they rely on the genetic material of host cells (our own cells). As we talked about in class, viruses are able to bind to our cell surface receptors and trick our cells to “let them in”. The viruses are then able to hijack our cells by releasing their genomes, or that information they couldn’t previously access, resulting in our cell making millions of copies of that genome to spread throughout the body in order to infect other cells and / or other human hosts. This is how all three of the coronaviruses hijacked our bodies and communities. Let’s hear what happened once this step occured.

SARS stands for Severe Acute Respiratory Syndrome. The SARS outbreak began in the Guangdong province in China in 2002. The coronavirus that caused SARS, called SARS-CoV, was likely spread to humans, in the China wet markets, from civets or other animals who acquired the virus from horseshoe bats. The World Health Organization (WHO) issued a global alert after identifying an atypical pneumonia spreading amongst hospital staff and later names the virus SARS based on the symptoms people began to express. The epidemic was controlled on July 5th 2003 and only four cases have been reported since, 3 of which being in a lab setting dealing with the specific coronavirus. The reason why SARS was able to be contained so quickly was due to the fact that one could only spread the virus if he/she had symptoms and if one expressed symptoms it was easy to self isolate, therefore not spreading the virus to others. In addition, SARS has a fatality rate of 9.6% meaning a good number of people who contracted SARS were likely to pass on and therefore not pass on the virus to others. 

MERS stands for Middle Eastern Respiratory Syndrome. As we learned in class, viruses are no longer named by their place of origin, but this was not the case in 2012 during the outbreak of MERS. Similar to SARS, MERS is a zoonotic virus, meaning MERS was passed from an animal, in this case a camel who contracted the virus from bat once again, to humans in Saudi Arabia. Although 27 countries have reported cases of MERS since 2012, transmission among people is rare and MERS has a fatality rate of 34.3%, making it even more deadly than SARS and therefore making it even harder to spread. 

The first case of COVID-19 or SARS-CoV-2 was reported in Wuhan China in December 2019. By the end of January 2020 the WHO had declared a public health emergency of international concern and by the beginning of February the WHO had declared a pandemic. So what makes the coronavirus disease so much worse than the other ones? How did COVID-19 spread so quickly and to the entire globe? And why are our daily lives changed forever or at least until we can get a handle on the virus?

First of all, the COVID-19 causing coronavirus SARS-CoV-2 is very similar to SARS-CoV, but with very unique and important differences. What we have all learned about SARS-CoV-2 is that you don’t need to be experiencing symptoms to transmit the virus. This is very different from SARS-CoV where you needed to have symptoms in order to transmit the virus. Also, while the transmission rates are lower for MERS and SARS because the fatality rates are higher, in the case of COVID-19, the fatality rate is approximately 1-3%, meaning more people are surviving COVID-19 making it easier for this virus to survive and pass on to other people that it has yet to infect. In addition, as we talked about in class, we have evidence that “viruses can naturally mutate to mimic host biology so as to ensure successful viral propagation” and as a result “a host of high frequency mutations have resulted in a least 5 differentiated SARS-CoV-2 strains to date” making it even harder to develop a successful vaccine to target and eliminate the coronavirus disease.   

So, will we ever be able to put a stop to the spread of the coronavirus disease and therefore the pandemic? The answer is yes, but we first need to figure out how to stop the spread of the virus. The truth about COVID-19 is that unfortunately, as stated above, it is much easier to transmit than SARS and MERS, and COVID-19 has been able to get on planes and travel the world unlike the previous coronaviruses. While it is easier to transmit it is also more survivable than the other coronaviruses that have impacted our communities thus far.

Can your common cold help you beat vicious COVID-19?

Season colds are quite common, and while they are inconvenient and make us feel icky, they may be our advantage for our battle with COVID-19. 

To start off, when reading this article, I noticed that the author used the term “coronavirus” more casually. He referred to a “coronavirus” as a common cold, which of course left me confused. So I dug a little deeper…

Here’s a fun fact that I learned from this:

Many of us having been thinking that COVID-19 is the same as what we call the “coronavirus.” After reading an article differentiating the difference between the terms, I found that the term coronavirus is actually the broad term to describe a whole range of viruses. SARS-CoV-2 is the specific virus that causes only COVID-19 and is causes what doctors call a respiratory tract infection.

Basic biology tells us that while there are many cells that make up our body, they are all interconnected. A pathogen, like the SARS-CoV-2 virus, is an enemy to the cell. We learned about how things enter the cell in biology: the pathogen enters the cell, travels through the cytoplasm, and enters the nucleus. Because the virus has genes, it is able to rapidly produce copies of itself to infect the other cells. And of course, we know how scary these infected cells are when they start spreading to the lives around us given our situation with a global pandemic.

What we now know is that the SARS-CoV-2 virus, our “bad guy,” can actually induce memory B cells. These memory B cells survive for quite a long time; they are important in identifying pathogens, and creating antibodies to destroy such pathogens. So when we got sick during the winter last year, chances are these memory B cells fought them off. The key part of the memory B cell in our fight against COVID-19 is the cell’s ability to remember the antibodies it created from past illness for the future.

What does this mean?

The belief is that anyone infected by COVID-19 already has the memory B cells from past common colds to fight the virus off.  Taking a further step, it is believed that since everyone already has the memory B cells, anyone who has had COVID-19 in the past is unlikely to get it a second time. If the SARS-CoV-2 virus were to enter your body a second time (which is likely considering the virus has not gone away and is literally all around us), our bodies would be prepared with former knowledge of the antibodies used to fight and win this time.

A study performed at the University of Rochester Medical Center is the first to demonstrate how this may be so.

Mark Sangters, Ph.D., is a research professor of Microbiology and Immunology at URMC; he has backed up his findings by comparing different blood samples. When looking at 26 blood samples of recovering moderate COVID- 19 patients (people who have had it for their first time now), it seems that many of them had a pre-existing pool of memory B cells that could recognize the SARS-CoV-2 virus and rapidly produce antibodies to destroy it. He also studied 21 blood samples of healthy donors, collected years before COVID-10 existed. What he found was that these B cells and antibodies were also already present.

When we are sick with a common cold, our antibodies are created by memory B cells to attack the Spike protein. This protein is what helps viruses infect our cells. What Sangters noticed, is that although each Spike protein is different for each illness, the S2 portion of the Spike protein is the same throughout all sickness. Our antigens can not differentiate the parts of the S2 subunit, so they attack the Spike protein regardless. This was his final piece in his conclusion that our common colds that caused our memory B cells to make antibodies, could be used to fight against COVID-19.

The Long Road Ahead:

My concern with this article is that this is the biggest issue we face with COVID-19 is patient outcome. As of right now, there is no way to fully prevent everyone from COVID-19 because it is still all around us. The issue the world is facing, is how to treat those who have already contracted the virus. This information just simply is not enough to help. How will these memory B cells help those who are currently sick? The answer: Scientists are unsure. There is still the uncertainty of the future vaccine and study of these memory B cells for a possibility of milder symptoms or shorter length of illness from COVID-19.

 

Despite all of this concern, this is still a step in the right direction. Any information about this terrorizing virus is still helpful given how little we know about COVID-19. If we were to expand more on this information, we could save the lives of those around the world!

 

 

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