STELARA – Monoclonal Antibody Therapy

Overview

According to their own website, STELARA uses the monoclonal antibody known as ustekinumab to treat patients of Chron’s disease. A monoclonal antibody is a synthetic antibody that originated in a lab animal. In order to make one of these special antibodies, a lab animal would be immunized and then have its B cells isolated and combined with malignant myeloma cells. The B cells and myeloma cells fuse in an aminopterin-containing medium, resulting in the creation of hybridoma cells. Hybridoma cells are important because they proliferate with the same epitope every time, which is crucial when creating a monoclonal antibody drug, as they will always serve the same function.

How does STELARA Work?

Once injected into the patient, the ustekinumab antibodies in STELARA function by binding to, and blocking, p40 protein subunits on the cytokines IL-12 and IL-23. Chron’s disease patients have been observed to have higher levels of these cytokines. By binding to the p40 subunits, STELARA inhibits the innate, pro-inflammatory actions of IL-12 and IL-23 by blocking them from binding to their intended targets. These targets and actions of IL-12 and IL-23 include the activation of natural killer cells and helper T cells, as well as the differentiation of helper T cells.

STELARA Side-Effects

  • Nasal Congestion
  • Sore Throat
  • Runny Nose
  • Upper Respiratory Tract Infections
  • Fever
  • Headache
  • Tiredness
  • Itching
  • Nausea and Vomiting
  • Redness at Injection Site
  • Yeast Infections
  • UTIs
  • Sinus Infections
  • Bronchitis
  • Diarrhea
  • Stomach Pain
  • Joint Pain
  • Serious Allergic Reactions
  • Lung Inflammation
  • Reversible Posterior Leukoencephalopathy Syndrome (RPLS)
  • Cancer

The function of STELARA is to suppress the immune response, thus, the patient is much more likely to contract minor and sever illnesses, such as TB. This is due to the body’s weakened ability to fight diseases while the immune system is suppressed by STELARA. While RPLS is seen more often in those taking STELARA, the company claims that the cause is unknown.

The side-effects of this drug are certainly scary, which is why doctor supervision and a prescription are required. It is fascinating how humans have the capability to engineer specific antibodies with specific epitopes so that certain diseases can be treated. It will be interesting to see if and how monoclonal antibody therapy is used in the future for treating more severe, life-threatening diseases.

Reviewing COVID-19 Tests

According to Stanford Medicine, the Stanford Health Care Clinical Virology Laboratory has developed a test for COVID-19. The test works by utilizing reverse-transcriptase polymerase chain reaction technique, which uses DNA primers to bind to the viral genome. This allows for the detection of envelope proteins and RDRP, both of which are characteristic of viruses. In other words, this test’s function is to identify viral RNA genomes. According to the University, the FDA relaxed its restrictions and established an Emergency Use Authorization mechanism for COVID-19 diagnostic tests on February 29, allowing this test to be implemented.

The Emergency Use Authorization implemented by the FDA also made the qSARS-CoV-2 IgG/IgM Rapid Test available for use, according to an FDA fact sheet. The Rapid Test measures IgG and IgM titers produced in response to COVID-19. Detection of IgM titers indicates that the patient has an active or recent COVID-19 infection. If IgG titers are detected, it indicates a past infection. If the two antibodies are detected together, it is likely that the patient had the infection and is still contagious.

Both sources make it clear that these tests are not 100% accurate, and false-positives may be a result. It is also unsure of how sensitive these tests are. With that being said, I think it was extremely important for the FDA to institute the Emergency Use Authorization. I understand that the organization likes to have more proven data to approve things, however, in a time when such large quantities of people are getting sick and dying, it is crucial that we do whatever we can to attempt to stop the spread of this disease. In my opinion, it would better for the tests to be false-positives and some patients are quarantined even if they are safe, than if there were no tests and people who had COVID-19 were unknowingly spreading the infection.

Modified T Cells Could Be the Medicine of the Future

According to the American Cancer Society, chimeric antigen receptor (CAR) T cell therapy is being further researched to discover how many types of cancer that this treatment can help to cure. CAR T cell therapy is a treatment in which a patient’s T cells would be extracted, followed by the addition of synthetic chimeric antigen receptors. The addition of these man-made receptors would allow the patient’s T cells to be better equipped to identify and bind cancerous antigens. Currently only certain lymphomas and leukemias have been approved to be treated with CAR T cell therapy, and the American Cancer Society says that further research is being done because certain cancers don’t display antigens on their surface, thus the CAR T cell would need a “special armor” to be able to identify the antigenic proteins within these other cancerous cells. I believe this research will be well worth the time and money invested as it could potentially save millions of lives and dollars, as the treatment currently costs between $450,000 and $1,000,000+. The side effects of CAR T cell therapy include neurotoxicity, destruction of host B cells, and possibly even cytokine release syndrome characterized by a flood of cytokines that causes a high fever and low blood pressure.

In addition to curing cancers, The New York Times writes that CAR T cell therapy could be used to treat heart failure. In this case, the CAR T cells would function by receiving receptors that bind to fibroblast activation protein on fibrosis of scar tissue. The concerns of treating heart disease with CAR T cell therapy are similar to the concerns of treating cancer with it — high fever and low blood pressure that is potentially fatal — and some scientists are even concerned with any treatment that attacks the host’s fibroblasts, so ensuring that this treatment only effects scar tissue is crucial. Currently, only testing on mice has been done, but the results were promising as the scar tissue appeared to disappear with the treatment.

I am curious to see what other diseases or injuries CAR T cell therapy could treat. For example, arthritis patients also suffer from fibrosis and it causes lack of mobility and stiffness in the joints. If the CAR T cell therapy could be specified to target the scar tissue in joints or on muscles, could we see a cure for arthritis? It would also be beneficial to continue the research of this therapy, as it will likely become a more affordable option for patients once we better understand how to perform this technique. In all, I believe that this treatment shows great promise for treating many diseases in the future.

How I’m Handling COVID-19

I would be lying if I said I wasn’t very concerned about the coronavirus when we departed for spring break. Luckily, I was not the one making decisions regarding society when the virus began to spread, as I severely underestimated this disease. Personally, I believe the decisions made by universities to move classes online was one that has potentially saved thousands of lives. Although college-age individuals are not as likely to die from the disease, and could often be asymptomatic, they are undoubtedly carriers of the disease. Keeping the students at the universities would be risking the lives of many of the older professors, administrators, staff, etc.

School from home has been interesting to say the least. Something about being in Chapel Hill in a university environment motivates me to do my work more so than a home setting. Probably because I’m surrounded by distractions at home. I also believe that classes via Zoom has been a good experience. While it may be easier to lose the attention of students, I ultimately believe Zoom allows those who don’t speak much in class are presented with more opportunities to voice their opinions. I’m also glad that professors have been understanding with students, and that acknowledging that having to work online can become inconvenient or difficult.

Dealing with the pandemic has become difficult as of recent. The “stay at home” orders in North Carolina definitely make life more monotonous, and make obtaining things more difficult. I’ve been working out from home and playing basketball in my driveway to pass some of the time. I’ve also been trying to get some extra sleep and to catch up on studying and notes. Hopefully the COVID-19 situation is solved quickly and managed in an effective way so that we all can return to our normal lives.

Image Obtained From: https://www.pittsburghmagazine.com/10-covid-19-memes-that-will-bring-a-smile-to-your-face/

Recent STD Prevention and Outbreak

According to the CDC, the United States has seen a record high in combined chlamydia, gonorrhea, and syphilis cases. The organization claims that chlamydia cases have increased by 3%, gonorrhea cases by 5%, and syphilis cases by an astonishing 14%! The CDC believes that there a number of reasons as to why there has been such a large increase in the amount of STDs reported in America. These reasons include drug use, cuts in funding for STD programs, and poverty. However, I believe the most important reason the CDC lists is the reduced practice of protected sex, especially with condoms. Using a condom is one of the most reliable methods to prevent STDs (apart from monogamy or abstinence) as long as it is used correctly.

While chlamydia, gonorrhea, and syphilis are generally seen as less serious STDs, similar prevention methods can be used to stop the transmission of more serious STDs such has HIV and AIDS. According to WHO, HIV and AIDS can be transmitted through unprotected anal or vaginal sex, blood, or by vertical transmission. It is important to practice safe sex because it is very effective at preventing the spread of HIV and AIDS. For example, WHO claims that condoms are about 85% effective at preventing the disease. Getting tested for STDs is also important so you can prevent spreading them to your sexual partner or children, as many STDs have congenital effects.

I believe that it is crucial to begin increasing funding and education for STDs so that transmission can be slowed. The CDC says that over half of “local programs” for STDs have experienced budget cuts. This is completely unacceptable, especially as these STDs, namely gonorrhea, begin to develop resistance to antibiotics. It is also important to continue educating younger individuals on the reliability of practices such as abstinence, monogamy, and the use of condoms or other contraceptives, as they become sexually active. I think that the best way to prevent the transmission and problems of STDs is not to scare people away from sex, but rather inform them of how to practice sex in the safest manner possible.

Growing Resistance – How Antibiotic Resistance is Increasing

While antibiotics are obviously essential in saving lives, and are without question a medical miracle, the effectiveness of these drugs is diminishing at what could be a rate faster than we know. There are a variety of types of antibiotics, each type equipped to target a certain feature of bacteria (i.e. peptidoglycan). However, because of the overuse and misuse of these medications, more and more pathogens are developing resistance to antibiotics. The use of antibiotics to grow livestock is another potential way that antibiotics are losing effectiveness. I believe that unless we move forward with extreme precaution, these drugs that are so essential in today’s medical world could be deemed useless.

According to the CDC, the estimated numbers of illnesses and deaths caused by antibiotic-resistant infections could be much higher than previously believed. The CDC also warns that two germs have been recently added to the “urgent threats” list. These germs are the “drug-resistant Candida auris” and the “carbapenem-resistant Acinetobacter.” On the positive side of things, the CDC claims that antibiotic-resistant illnesses in hospitals decreased by 28% from 2012 to 2017. The group is also investing millions of dollars into research on prevention strategies for these antibiotic-resistant illnesses, as well as working cooperatively with the FDA and private industries to ensure that we have effective antibiotics for as long as possible.

The CDC also addresses antibiotic use in the agricultural industry and how it correlates with antibiotic-resistance. They realize that antibiotics are used for “growth promotion” and “feed efficiency,” and these techniques undoubtedly contribute to antibiotic resistance. Therefore, in 2017, it was made illegal to use medically important drugs in these strategies in the United States. I am curious to see how this policy is utilized when regarding imported meats. Other reasons that antibiotics are used in animals are to cure, control and prevent disease in animals and livestock. I believe this to be important in the control of zoonotic diseases.

Antibiotics have been used to grow and feed livestock more efficiently, however, in 2017, the use of medically important antibiotics in growing livestock was deemed unlawful.

Global Prevention of Polio via the IPV and the OPV

Although polio is said to be eradicated in the United States, it has not yet been eradicated globally. According to the CDC, certain Asian countries are currently experiencing polio outbreaks, and “enhanced precautions” should be practiced if traveling to these countries. These precautions include receiving the series of polio vaccinations before traveling if you have not yet received them, or receiving a booster dose of the polio vaccine if you were vaccinated a child but are now an adult. The recommended booster dose is the inactivated poliovirus vaccine (IPV). In addition to the vaccine recommendations before traveling to these countries, the CDC also says that “The World Health Organization recommends that these countries require residents and long-term (4 weeks or more) visitors show proof of polio vaccination before leaving the country.”

Countries in red are those in which the CDC recommends receiving a polio booster vaccine before visiting.

The CDC has also developed a strategy in which they believe will be able to eradicate polio across the globe. This plan, known as the “Global Polio Eradication Initiative Polio Endgame Strategy 2019-2023”, intends to rid the world of poliovirus through “eradication, integration, and containment/certification.” Polio has three wild types, and type 2 was announced as eradicated in 2015. The remaining 2 wild types are set to be eradicated through a bivalent OPV that targets types 1 and 3. Once everyone is vaccinated through OPV or IPV, the CDC wishes to contain poliovirus in only research and medical facilities, and slowly diminish the amount of facilities that the virus is held in, until eventually all wild types of poliovirus are eradicated. If done successfully, modified versions of poliovirus will be implemented into IPVs and OPVs to make safer vaccines for global use.

Based on what I have read about the CDC’s plan for global eradication of polio, I believe that they are headed in the right direction, however I believe that it may take longer than anticipated. The main reason for my doubt is the current situation in Asia which I wrote about. There are still people in other countries that are either unavailable to afford the vaccine, or they simply don’t want it. I am unsure of how the CDC and other organizations will be able to afford supplying these vaccines and boosters to everyone in the world. Therefore, there are still hosts that are susceptible to the disease, and outbreak is obviously still a possibility. I believe once we see these outbreaks stop, and the issue of making sure every person is vaccinated, the plan will be able to be executed well.

Works Cited:

Picture obtained from CDC

Beneficial Bacteria – A Look at the Human Microbiome

The collection of bacteria that ordinarily inhabit your body are know as your microbiome. These bacteria can play a role in your bodily functions such as digestion and immune health. However, a disruption of the human microbiome can also occur and allow for diseases such as Clostridium difficile infection. It is important for humans to advance our understanding of the microbiome so that we know the exact functions of all these bacteria. We must also learn the causes of these disruptions (such as overuse of antibiotics) so that we can minimize their occurrence and further prevent disease.

Recently, a team of researchers from the Stanford University School of Medicine discovered that the human microbiome is “churning out tens of thousands of proteins so small that they’ve gone unnoticed in previous studies.” According to the researchers, these proteins can be organized into over “4,000 biological families.” The proteins are believed to play a number of roles for the bacteria, but the one I found most interesting was the fact that many of these proteins are predicted to be involved in bacterial warfare. It would be interesting to see if an extraction of these proteins would allow for more effective antibiotics. The team believes that since the proteins are “fewer than 50 amino acids in length,” they were likely folded into unique shapes and overlooked as actual proteins, but if the “shapes and functions” can be recreated in lab, then they are likely to advance drug development.

According to a recent study by Northwestern University, it may be important to look at “host ecology” when conducting microbiome research, particularly of the gut. The study examined how “Old World monkeys like baboons” have gut microbiomes more similar to humans than those of apes such as chimpanzees, which are more closely related to humans genetically. The researchers claimed that since the Old World monkeys have a more similar ecology and physiology to humans, then they should be used when studying the human gut microbiome. I think it would be interesting to know exactly what differences in habitat, diet, etc. would result in different microbiome compositions. It is also interesting that these researchers believe ecology is more important than genetics when looking at the gut microbiome, and makes me curious about whether there are different gut microbiome patterns between different cultures and ethnicities because of the same ecological differences? Hopefully future research answers this question.

Baboons are believed to have more similar gut microbiomes to humans because of similar “host ecology.”

Why Get Vaccinated for Influenza this Year?

If you begin to have a fever, malaise, lethargy, headache, sore throat, nasal congestion, or a cough, you may have the flu. Influenza is a segmented, single-stranded RNA virus with an envelope. What does this mean to the general public? The envelope means that the influenza virus is susceptible to disinfectants and detergents, so washing your hands for about 20 seconds is a simple way to prevent the flu. It also means that since the flu is segmented, it is able to rapidly change by reassortment, and it is also highly communicable. Antigenic drift, or when surface proteins on the viroid change, and antigenic shift, the development of a new strain of virus, allow influenza to prevent immunity. The constant change of flu strains means that each year certain strains are going to be more prevalent and cause illness, thus we must come up with new vaccines every year.

graphical, representation, ultrastructure, specific, seasonal, avian, 2009, H1N1, virus
This is a model of a typical flu viroid. The protrusions from the envelope are the hemagglutinin and neuraminidase spikes. The hemagglutinin spikes are responsible for binding to host receptors and are different between flu strains because of antigenic drift (caused by RDRP).

According to the FDA, there are nine different manufacturers that have had flu vaccines released by the FDA for the 2019-2020 season. The FDA recommends that you get a trivalent vaccine that protects against three strains of the flu, or a quadrivalent vaccine that protects against four. The three main strains the FDA believes vaccines should contain on this season are: 1. “an A/Brisbane/02/2018 (H1N1)pdm09-like virus.” 2. “an A/Kansas/14/2017 (H3N2)-like virus.” and 3. “a B/Colorado/06/2017-like virus (B/Victoria lineage).” In the case of the quadrivalent vaccines, the FDA also recommends including a strain of “a B/Phuket/3073/2013-like virus (B/Yamagata lineage).”

The variety of strains included in these vaccines decreases the probability of you getting the flu by protecting against multiple flu viruses. While it is not guaranteed that the vaccine will prevent you from getting the flu, it is known that flu vaccines do not cause influenza. Therefore, I believe you should play it safe and get the vaccine to at least expose yourself to some flu viroids in order to allow your immune system to prepare for the flu if you do contract it. I would say it is better to get the vaccine and not get the flu than to not get the vaccine and die because of the flu or secondary infections caused by the disease. The CDC even estimates that “from October 1, 2019, through February 1, 2020, there have been 12,000 – 30,000 flu deaths.” A large number of these deaths probably occurred in individuals who did not receive an influenza vaccine. The CDC also believes that this year’s vaccine is somewhere between 40%-60% effective. As the vaccines this year are moderately effective, everyone should go get the vaccine in my opinion. The vaccination is quick and affordable, if not free, so there is no reason to not get it, unless you are highly immunocompromised.

Andrew Wakefield, Autism, and the MMRV Vaccination

Background of the Wakefield Study

In 1998, a gastroenterological surgeon by the name of Andrew Wakefield had an article published in The Lancet, a medical journal based out of the United Kingdom. Wakefield’s study argued that the MMR vaccination was a cause of autism in children. However, according to an article by the GI Society, Wakefield’s research was fueled by personal profit and consisted of numerous flaws and acts of misconduct that made the study unreliable. Regardless of the research that has been done to refute the claims of Andrew Wakefield, including The Lancet retracting Wakefield’s original publication, his work was enough to convince a considerable number of parents to become “Anti-vax.”

Problems and Purposes of the Study

One of the fundamental errors of Wakefield’s study was that he used a sample size of only 12 children. To make matters worse, he selected these children specifically because they had known gastrointestinal and developmental issues. In order to provide a reliable study, Wakefield would have needed a sample of hundreds if not thousands of people, and would have needed to choose at random, thus providing a sample that can give statistically significant results. As a matter of fact, other researchers performed similar studies only to find inconclusive data, and failed to establish a causal relationship between the MMR Vaccine and autism. While Andrew probably knew that random-sampling and a larger sample were necessary, he avoided these tactics because he published the study for financial gain. Wakefield was being paid by a lawyer of one of the autistic children’s parents’ in return for helping the lawyer win an anti-vaccine lawsuit. He also led a non-profit in which he was secretly profiting $300,000 per year, and planned to release his own MMR vaccine for profit as well. When considering these facts today, it should be clear to see that the original MMR vaccine is safe and in no way should be avoided.

Andrew Wakefield used corrupt, unethical methods for personal financial gain.

Why Get the MMRV Vaccine?

According to the FDA, the United States is still experiencing outbreaks of the measles, despite being declared “eliminated” in 2000. While the Wakefield allegations caused skepticism about the vaccine and resulted in “anti-vaxxers”, it should be known that the MMRV vaccine has been approved in the United States for about 5 decades now. The ideal way to prevent outbreaks of the contagious illnesses the MMRV protects against would be to have as many people as possible vaccinated, if not everybody. When a large proportion of the population gets vaccinated (about 90-95%), herd immunity is provided to the community and outbreaks become seemingly impossible. The dangers of measles, mumps, and rubella should not be underestimated, and by simply getting a vaccination that is proven to be safe and efficient, these diseases can be suppressed.