BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: #antigens

Optimus Prime, Megatron, Proteins? The New Transformer Vaccine Candidate!

Amid the global outbreak of COVID-19, with no end in sight after nearly two years, the future wellbeing of humans is in danger. Coughs, fevers, and shortness of breath have lent way to millions of deaths across the globe. As thousands of researchers relentlessly work to find solutions to this virus, multiple vaccine candidates have emerged. Specifically, in the United States, millions of Americans have received doses of the Pfizer-BioNTech, Moderna, and Johnson & Johnson’s Janssen vaccines. However, scientists at Scripps Research recently recognized a new, self-assembling COVID-19 vaccine as a potentially more efficient and effective way to fight this worldwide battle.

 

Primarily, it is critical to understand how vaccines function as they help protect the immune system. The COVID-19 vaccines currently in effect are mRNA-based; in other words, the messenger RNA signals one’s body to produce a harmless viral protein that resembles the structure of a spike protein. The body, with the help of T-Helper cells, recognizes this structure as a foreign invader as B cells bind to and identify the antigen. The T-Helper cells will then signal these B cells to form B-Plasma cells and B-Memory cells. When getting the vaccine, the B-Memory cells are especially important as they prevent reinfection. This is a process known as adaptive immunity. Here, in the event of future infection with the spike-protein COVID-19, the memory cells would help carry out the same response more quickly and efficiently. Essentially, this process acts as the body’s training in case of any future infections.

 

While the Scripps Research COVID-19 vaccine would evoke a similar immune response to that described above, it differs from other candidates in how it assembles in the human body; this new vaccine would be comprised of proteins that are able to self-assemble. On their own, these nanoparticle proteins would transform into a sphere protein structure surrounded by smaller proteins, mimicking the coronavirus’s shape. Here, the self-assembled spike proteins are more sturdy and stable than in an mRNA-produced structure. Thus, it more accurately prepares the body for future infection with COVID-19. In fact, multiple tests found that mice who were given the experimental vaccine were able to fight off not only SARS-CoV-2 but also SARS-CoV1 along with the alpha, beta and gamma variants.

 

Nonetheless, influencing the public to get a newer vaccine instead of the well-trusted vaccines already in production requires proof of the candidate’s benefits. Primarily, as mentioned, early results find that this new candidate would perform well with many different strains of COVID-19. Additionally, researchers assert that this vaccine would be relatively simple to produce on a mass scale. Lastly, scientists found that this vaccine may well be more protective and long-lasting than current vaccine candidates. Although the process of vaccine approval is lengthy and often difficult, I am hopeful for the future of the Scripps Research vaccine if it is put into production. Moreover, I believe that such experimentation with self-assembling nanoparticle proteins transcends the current pandemic. The benefits of this field present a wide array of opportunities, and I look forward to seeing what its future may hold.

 

What do you think? Are these transformer-like self-assembling particles a gateway to the future of medicine or an unnecessary distraction from effective treatments already in circulation?

Suleman Hussain’s Journey into Biomedical Research

Antigens are foreign substances which induce an immune response in the body, especially the production of antibodies. The antibodies then latch on to the foreign substance in an attempt to mark them to be destroyed. This ability to bind to specific molecules makes antigens ideal probes in cell research, where they are used to latch onto, and thus help isolate and identify, molecules of interest in and on cells. Suleman Hussain, a researcher in the lab of Daniel Higginson and Simon Powell at MSK, discovered a novel and efficient way of preparation, fixation, and embedding of tissue for electron microscopy.

His research proved that Antibodies raised against aldehyde-fixed antigens improve sensitivity for post-embedding electron microscopy. To prove their hypothesis, he and his team immunized rabbits with antigen pre-fixed with glutaraldehyde (GA, which is commonly used in electron microscopical investigations). The results were consistent with their hypothesis, thus marking the discovery that will improve future biomedical research in terms of efficiency.

Despite all of his accomplishments, Suleman Hussain has experienced numerous hardships due to his sexuality. Being a member of the LGBTQ community, Hussain had trouble finding himself. He lived in India where homosexuality was criminalized so he kept his true self under covers, hidden from the rest of the world. Hussain grew up Muslim so to this day, his family still doesn’t know that he’s gay or that he’s married. “But I have grown more comfortable and more confident in myself. At this point, if they somehow find out then I’m ready for it.”

The reason why visibility of LGBTQ people in science is so important is because we serve as examples to gay teens, who go through a lot. For them to be inspired to do what they are really capable of, that’s what motivates me to be visible. It’s become much easier now overall than what it was before, but still there are a lot of homeless LGBTQ teens and higher rates of suicide too. So in that sense it’s very important for them to have examples.

-Suleman Hussain

At the Coronavirus Drive-Thru: Which Test Would You Order?

As the world faces the Coronavirus pandemic testing has become a hot issue that people are facing in their daily lives.  But the question remains, which test is best?  It is likely that we will never know the answer to that question, but an understanding of the options available can certainly help the general public to make an informed decision before selecting a method of testing.  According to the article from the Financial Times, titled “What coronavirus test does the world need to track the pandemic?” there are two main types of tests for the virus officially named Sars-CoV-2: Antigen tests and Antibody tests. Antigen tests are used to detect whether or not an individual is infected with the coronavirus that causes Covid-19 while antibody tests are used to determine if an individual has been infected in the past.

Antigen tests come in two varieties, a rapid version that delivers results in minutes and another using Polymerase Chain Reaction (PCR) to multiply the genetic material found in a virus containing sample from an infected individual which takes longer.  Both the rapid and the PCR tests can be performed on a sample collected using a nasopharyngeal swab but can also be done using a throat swab or saliva sample.

The virus can be detected as early a the first day of symptoms but is most accurate in the first week.  This is measured by the cycle threshold where the lower values indicate positive results.  No tests are always accurate but the rapid tests have been found to have more false positive and negative results than the PCR tests.  In a study performed by Vermont’s Department of Health only four individuals of 65 who had tested positive with the rapid test, also tested positive with the PCR test.  Because of this many states require both tests to confirm a positive diagnosis.  Unfortunately, the PCR tests have also shown high incidences of false negatives.  Regardless of which test is used, the accuracy still seems to be connected to the manufacturer of the test itself. Since the PCR test is thought to be the most accurate because it detects the presence of the genetic material of the virus, it is less likely to provide a false positive.  As result, these are best used to identify infection as opposed to letting an individual know that they are not infected.

Antibody tests require a blood sample in order to detect the presence of antibodies against Sars-CoV-2 because once an individual is infected with the virus their immune response creates IgM antibodies that are present close to the time of infection and IgG antibodies that are produced longer after infection.  These antibodies are proteins produced by the white blood cells that help to fight the virus, so if they are present in an antibody test, is clear that the individual has already been infected.  When an individual is infected with a virus, lymphocytes called B cells are triggered by the presence of the antigen of that virus, and bind to the antigen using an antigen receptor.  This then causes the production of cells that produce proteins called antibodies which have the same shape and structure as the antigen receptors of the B cells making them helpful in directly defending against antigens present in body fluids. Antibody tests provide a quick result and are preferred because they help people to determine if a person can return safely to society with less risk of infection.

As the pandemic became a global issue many tests began to be developed but the antigen tests were more commonly performed in the public while the antibody tests were reserved for private companies due to the need for more materials like swabs and reagents to perform the tests.  Both tests are being created all over the world but some countries are producing more than others and the US was slow to get started but has increased production more recently. Because the tests must be of good quality, and the staff that are using them must be trained well, it is hard to produce them fast enough.

 

Could Rapid Testing Be the Key to Beating COVID-19?

A study published by University of Colorado Boulder and Harvard University researchers, states that rapid tests could help the world come close to eliminating COVID-19. The study focused on whether sensitivity of the tests, or turnaround times of getting the results is more important. By using mathematical formulas, different scenarios and three locations (a 10,000 person population, a university setting and in a large city) they came to conclude that when trying to slow the spread, frequency of testing and turnaround time is more important than the sensitivity of the test.

It is important to note the difference between the PCR test and the rapid antigen test. A PCR test, which uses polymerase chain reaction technology (hence the name) to detect traces of the virus’ genetic material. A rapid antigen test does not trace the genetic material but instead looks for specific proteins on the surface of the virus, known as antigens. A PCR test can detect one SARS-CoV-2 RNA molecule for a positive test result, the rapid antigen test needs thousands of virus particles for a positive test result. An antigen is present on the outside of a pathogen. In adaptive response to pathogens, dendritic cells place these antigens on display. The antigens are what allows the T-helper cells to recognize the antigen and trigger the cell mediated and humoral response. Therefore, if your body is fighting against COVID-19, the antigens would be displayed on cells and the rapid test may recognize them.

In one of the scenarios a large city had widespread rapid testing two times a week and they reduced the infections by 80% compared to widespread PCR testing done two times a week that only reduced infection by 58%. This scenario shows that because two thirds of infected people do not show symptoms as they wait for their results they are not quarantining. If people receive the positive tests results sooner, they can self-isolate sooner.

People have felt hesitant about rapid testing since it is less accurate than PCR testing and may miss cases where levels of infected particles are too low. However, it has been shown that there is a short time period where PCR testing will show a positive, and rapid tests won’t. This is because infected particles can go from 5,000 to 1 million in less than 24 hours. During this short window of time it is also likely that the patient is not contagious yet. 

Personally, I think that having more accessible rapid tests will be a huge help to curbing the virus. Even with less sensitivity, if a person tests positive then they self-isolate up to up to 48 hours quicker, if tests results take longer, then even more. This means that less people will get infected. I know that when family members have gotten tested, especially in the beginning of the pandemic, tests took 5 days when the labs were backed up. If they had not been properly quarantined during the 5 days, this could pose a danger to others. Therefore, I think that the accuracy can be put aside for the speed of the test results.

So, what do you think? Is rapid testing the inexpensive, fast, key piece to curbing the infection rate, or is the accuracy of tests more important?

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