BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: vaccines

20 VS. 4- A Universal Flu Vaccine

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20 VS. 4- A Universal Flu Vaccine

 

Every autumn, it’s the same routine: scientists predict which 4 or 5 strains of influenza will be circulating in the coming months, prepare a vaccine, and those who want it get it; sometimes the predictions are accurate, and people are spared from the virus, but other times it is not. 

 

As we have learned in AP Biology, the human body has both innate immunity and acquired immunity to protect against diseases; vaccination is a form of artificially acquired immunity, in which a vaccine introduces the immune system to proteins from a virus; this trains the immune system to produce antibodies against the virus, so it knows how to encounter the actual virus later, should it be necessary. Unfortunately, when it comes to the flu vaccine, the antibodies that we are trained to produce from the vaccine are often not a match for the circulating flu strains, which causes the vaccine to be less effective.

 

But what if there were a way around this? Suppose that, instead of having to play a delicate guessing game as to which flu viruses are circulating more than others, there was a single, comprehensive vaccine that could provide immunity for multiple strains at once. This may be a real possibility in the near future; in November 2022, a research team at the University of Pennsylvania designed an influenza vaccine using mRNA technology, and when tested in mice and ferrets, was discovered to protect against 20 different strains of influenza. 

 

One may be wondering, how could such a feat be possible? Well, we must look at how this specific vaccine was designed; it was made in a very similar fashion to the COVID-19 Pfizer and Moderna vaccines, using mRNA technology. When a person takes the Pfizer or Moderna vaccine, mRNA is introduced into the person’s body, triggering their cells to recreate a harmless version of the spike protein, causing the person’s immune system to recognize it and therefore learn how to create an efficient immune response against the virus. 

 

The fact that this has been seen in the COVID-19 vaccine makes it easier to understand why the mRNA vaccine created for influenza was effective in mice. This is very different from the traditional influenza vaccine, which involves injecting an unactivated or weakened version of the virus into the body; while it is a formidable opponent against the influenza when the strains are a match, the design of traditional vaccines have been found to be less protective than mRNA vaccines. 

 

The experimental 20-strain influenza vaccine has yet to undergo human trials, but it does provide some optimism looking into the future of flu seasons.

A New Hope? Promising new research finds a way to treat COVID-19

Despite the recent decline in COVID-19 cases, researchers and public health officials struggle to treat and prevent new cases of the disease.  A 2022 article in the Washington post outlined the recent efforts by researchers to treat and prevent COVID-19, particularly examining monoclonal antibody treatment, a treatment that utilizes human-made antibodies to aid in the Body’s natural response.

However, according to researchers, new mutations are quickly arising which undermine the effectiveness of these treatments, making it difficult for the medical world to keep up with the virus, so biologists are turning to more novel methods.  One Quebec-based company, Sherbrooke, thinks they’ve found the solution, “We saw a sharp decline in viral loads,” says the company’s chief medical officer Bruno Maranda.

Traditional monoclonal antibody treatment has had trouble inhibiting the binding between the spike protein of the virus SARS-CoV-2 and human cells because the binding location of the spike protein is mutating quicker than researchers can adjust antibody treatment.  According to Andrés Finzi, associate professor at the University of Montréal, “there is a huge immune pressure on the virus,” indicating that it will likely continue to mutate in this way.  

 

Novel Coronavirus SARS-CoV-2 Spike Protein (49583626473)

 

 

However, scientists have noticed that certain areas of spike protein have remained rigid as the virus mutates; one such area is the stem helix.  Because of its lack of mutation, scientists believe that this area is essential to SARS-CoV-2 and if disrupted can limit its ability to mutate and cause harm to our bodies.  

Although the new drug from Sherbrooke uses 2 antibodies that attack the spike protein in a more conventional way, the new third antibody attacking the more rigid areas of the protein has proven effective in all trials that have been undertaken.

Another recent paper has also attempted to amend antibody treatment to target more stable sections of the spike protein: the fusion peptide.  According to the chief of the Antibody Biology unit of the National Institute of Allergy and Infectious Diseases, this structure “acts like a grappling hook and inserts into the human cell membrane, pulling the membrane closer to the virus membrane.”  Researchers hope to use these rigid structures to help develop more reliable treatments and preventions for COVID-19.

This system of antibodies protecting our bodies from illness is similar to what we are currently learning in Biology class.  In class, we learned that in the body’s humoral response to pathogens, B-plasma cells secrete antibodies that bind to pathogens, thereby neutralizing them, allowing them to be quickly engulfed by macrophages and destroyed.  Monoclonal antibody treatment leverages this function of antibodies, creating artificial antibodies to facilitate this interaction more strongly.

While these new developments in COVID-19 treatment are exciting, Finzi warned that “we shouldn’t underestimate the capacity of a coronavirus to mutate.”  Other scientists, including Harvard professor of pediatrics Bing Chen, believe that antibody treatment research should not take the place of other disease-fighting tactics; according to Chen “we need much more effective vaccines, for sure.”  But one thing remains true, and that is that SARS-CoV-2 continues to mutate, and will continue to be a serious problem if we fail or adequately treat and prevent it, and while the number of cases is decreasing, it still remains strikingly high for us to write off the disease as harmless.

Do Vaccines Really Prevent Viruses?

Researchers from the University of Birmingham have shown that T cell immunity is coping with mutations that have increased within COVID-19 variants. Researchers tested CD4+ T cells at the beginning of the pandemic and found that a few of the T cells were able to recognize the epitopes in the Omicron variant. As SARS-CoV-2 continues to mutate, T-cell recognition of epitopes could decrease, causing a decline in the overall protection of the immune system. Although most people have a diversified T-cell response against the virus, some are less effective against Omicron specifically.

Vaccines developed at the beginning of the pandemic help to provide strong protection against severe hospitalization and death. But COVID-19 and SARS-CoV-2 continue to mutate. These mutations alter the epitope, which the virus uses to enter. It helps the virus to dodge the immune system’s attack. Current vaccines help the creation of antibodies and immune cells that recognize the protein. 

Vials containing the Moderna COVID-19 vaccine sit on a table in preparation for vaccinations at Kadena Air Base, Japan, Jan. 4, 2021. As part of the DoD strategy for prioritizing, distributing and administering the COVID-19 vaccine, those providing direct medical care and emergency services will be prioritized to receive the vaccine at units based in Japan, including Kadena AB. (U.S. Air Force photo by Airman 1st Class Anna Nolte)

One thing we have learned thus far in AP Biology class is that T Helper Cells stimulate other T cells to divide and create two types of cells. T Memory Cells are long-lived cells to prevent reinfection, and T Killer Cells or Cytotoxic T Cells kill infected or cancerous cells. 

It is very interesting for us to be able to understand how vaccines work to help us. Current mRNA vaccines produce some T cells that recognize multiple variants. This may help to protect against severe disease with the Omicron variant. Hopefully, with continued research, they will be able to make another vaccine that can specifically enhance this T-cell response. 

Is the recently discovered hidden cavity on the SARS-CoV-2 protein a target for drugs?

Many of us have been vaccinated against COVID-19 and have had the virus, leading us to become used to the virus being prevalent in our lives during the past few years. Even though a successful vaccine has been rolling out for a while now, new therapies have not yet been discovered for future strains. Finding new therapies for the virus remains a major priority in the field of science, even if many of us have been protected already. This issue remains a priority because new variants and strains have been continuing to emerge, and some resist present therapy mechanisms.

SARS-CoV-2

The most effective approach to attempting to combat the virus is addressing the proteins on the surface of therapeutic targets, known as spike proteins. The spike protein (S proteins) located on the surface of the virus leads to its spiky protrusions, and its mechanism to enter human cells. Like we learned in AP Biology class, the spike proteins of the virus latch to cells by matching with a specific receptor on a cell’s surface. The spike proteins of the virus have to latch on to the new cell to infect. Successful messenger RNA vaccines properly target this spike protein, which is the main goal when creating new therapies for viruses. 

                                             Spiky appearance of SARS CoV-2 virus

Luigi Gervasio, a chemistry and structural/molecular biology professor at University College London, and his team have been working towards addressing this issue. By partnering with the University of Barcelona’s research team, the two teams took the first steps to discover a possible mechanism for future drugs to detect and protect against the SARS CoV-2 Virus. Through thorough research and investigation, they uncovered a “hidden” cavity on the surface of a prominent infectious agent of the virus known as Nsp1. The team was able to make this discovery by testing small molecules that had the potential to bind to the Nsp1 cavity. The team identified one, 5 acetylaminoindane, which is essential for the development of new drugs against viruses. They concluded that this cavity permitted the calculation of the cavity’s atomically spatial arrangement, which will allow the development of these drugs.

The results of their breakthrough findings set the stage for developing new therapies that will be able to target the NSp1 protein against SARS-CoV-2 and present Nsp1 proteins in future coronavirus strains. Not only will this finding be impactful for targeting SARS-CoV-2 and future variants, but also new cavities on the surface of other proteins that have yet to be found by scientists. Finally, this research is monumental for both SARS-CoV-2 and virus treatment in years to come!  

 

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?

Mu Vs. Delta: Which is the Scarier SARS-CoV-2 Variant?

The Mu variant has been a term of interest in a lot of peoples conversations. This is due to the fact that it has been getting a lot of news coverage as one of the latest variants of the world wide virus SARS-CoV-2. It has been portrayed to be the next big virus ready to take over the world, but, does it have the legs to do so and how much more dangerous is it than other mutations such as the Delta variant?

Laboratoire de Physique de la Matière Condensée laboratoire PMC - 46940329992

The Mu variant first popped up on January 2021 in Columbia and has spread to about 39 countries since then. Mu is very similar to the original version of the SARS-CoV-2 virus. However, where it differs is at the two mutations E484K and K417N. These are what cause Mu to be seen as a variant of the original virus. The traditional anti-bodies that would normally be able to stop SARS-CoV-2 are seemingly ineffective against Mu leading the World Health Organization to classify it as a “Variant of Interest”. This classification means that it will continue to be monitored closely to derive the best possible plan on how to contain it. The mutations of Mu give it different properties such as mutation E484K, this mutation caused a drastic change in the structure of the original Covid-19 protein and thus made it so that it is able to by pass the human immune system easier. This is seen as a big problem because studies of how the anti-bodies effect SARS-CoV-2 conducted in US and UK compared to those conducted African countries have shown that African cases seem to be severely less effective against SARS-CoV-2. Researchers believe this is due to Africa being exposed to significantly more cases with the E484K mutation. As discussed in class this sequence of numbers and letters means that in the original amino acid sequence at spot 484 there was a Glutamic Acid amino acid (which is a negatively charged), and then once the mutation occurred it then became Lysine which is positively charged. This change in properties is what causes the protein to fold differently thus causing a severe changes as to how it behaves in humans. The Mu variant seems to have been able to disregard the anti-bodies and still effect the human body. However this seems to be the reach of its dangerous mutations because as of now scientist have no reason to believe that Mu is any more transmissible than the original virus which is a good sign.

The Delta variant has been an extremely worrisome mutation for some time now with the first case being noted back in October of 2020 believing to have originated in India. The Delta variant has been one that has taken over the world recently and it seems as though the former version of Covid-19 is a thing of the past and that Delta is the new pandemic. This is due to Delta’s interesting mutation P681R. The original amino acid at place 681 was Proline which has no charge, however after the mutation occurred it became Arginine which is negatively charges causing the amino acids to behalves differently with each other and the environment. This mutation is the cause of Delta’s incredibly rapid spread throughout the world. This ability to be globally spread in months is just one of the reasons why it has also taken the lives of so many as more people are getting Delta over the initial virus now.

Ultimately, it is clear which variant has been seen as the more dangerous by the media: Delta. However, while the Delta variant is scary in it’s own right, it just seems to be a faster spreading SARS-CoV-2. Meanwhile Mu has a way to almost be a completely different virus as it spreads just as fast as the original virus (it only took 4-5 months to completely shut down the world). It is also able to completely bypass the anti-bodies if you already had Covid-19 or have the vaccine. If this virus reaches levels of spread to the likes of Delta then scientist are going to have to create a new vaccine for Mu as it is simply to dangerous to ignore. Feel free to share how you feel about all of this and let me hear your take on the more menacing variant!

A New Way to “Tangle” with Diseases? British Scientists Think They’ve Stumbled Upon the Future

A team of scientist from the Universities of Bath and Birmingham have made a discovery that is making noise in the world of Biology. Ironically, they had the realization while studying silent mutations in DNA. What they found is a new method of evolution. Well not a new method per say as the scientists predict this method is being used in all forms of life; however, new in the sense that it was only recently realized. What they have discovered is a trend of tangles in DNA strands. This tangling occurs in DNA strands that are not in a double helix as DNA typically is. However The DNA strands are separated during copying. This task is done by DNA polymerase enzymes. During the copying process, the enzymes are often disrupted by the tangles in the strand. The resulting skipping of genes causes specific mutations to the DNA.

DNA replication split horizontal

The scientists then tested their hypothesis by way of experiment. They did so by studying the evolution of soil bacteria called Pseudomonas fluorescens (SBW25 and Pf0-1). They began by removing the gene that give the bacteria the ability to swim. They then observed the re-evolution of the strains to regain the ability swim. Both strains evolved quickly; however, there was a clear differences in predictability. One strain (SBW25) mutated the same part of a particular gene in every trial. The other strain (Pf0-1) varied in which gene and where the mutation occurred in each trial. Upon further observation, this contrast coincided with a hair-pin shaped tangle in the SBW25 strain. As the DNA polymerase enzymes would pass this tangle they would be effected in a predictable manner that would disrupt copying of DNA and result in a mutation that allows for the bacteria to swim. The scientists tested the theory by removing the tangle. They did so using 6 silent mutations so that the DNA sequence would not have a relevant change. The trials after the change showed that both strains showed inconsistent areas being mutated.

 

DNA are the dictators of protein synthesis in the body. The DNA sequences code for the types of proteins that are created. Proteins perform many of the bodies function. This means that even the slightest change in the sequencing of DNA can have major effects on the functioning of a human body or any organism. The process of evolution was thought to be caused by random errors in DNA sequencing that coincidentally gave an organism a survival advantage. These mutations would then be tested in the concept of survival of the fittest. While this is still thought to be the most prevalent form of evolution, especially with eukaryotic organisms, the tangling of DNA strands proposes a form of evolution that would be easier to study and predict.

 

The predictability of such a phenomenon is where the intrigue in viruses arises. “If we knew where the potential mutational hotspots in bacteria or viruses were, it might help us to predict how these microbes could mutate under selective pressure.” says Dr. Tiffany Taylor, from the Milner Centre for Evolution. Mutational hotspots have already been found in cancer, and the new information on their significance is getting scientists excited about the opportunities present. The new ways to understand and predict evolution of bacteria and viruses may allow scientists to be a step ahead on vaccines and be able to anticipate and understand new variants. It’s hard not to think this information would’ve been nice before the rise of SARS-CoV-2.

Dr Jessie Price: Her Impact on the World of Vaccines

Dr Jessie Price, a black female veterinary microbiologist who changed the veterinary field for the better.

Dr. Price’s Path to Success: Academic Life

Born January 1, 1930, Dr. Jessie Price lived in Montrose Pennsylvania with her mother Teresa. Teresa Price was a huge motivator for her daughter’s success and pushed her daughter to flourish academically. As an adolescent, Dr. Jessie Price attended surrounding public schools, all were predominantly white. During this time, it was typical for graduates to jump into a career to support their families, however Teresa Price valued academics greatly and supported her daughter’s notable academic talent. Dr. Price attended the College of Agriculture at Cornell University, where her tuition was covered by her resident status, as she spent a year in Ithaca taking more classes at a nearby high school after graduation. Her goal to attend medical school was not met due to financial costs, however, she found her passion in microbiology. In 1953 she earned her bachelors degree in microbiology, then returned to receive her masters degree in veterinary bacteriology, pathology, and parasitology in 1956. in 1959, the same year she received her masters degree, she earned her Ph.D after completing her dissertation, “Studies on Pasteurella anatipestifer Infection in white Pekin Ducklings” published by the Journal of Avian Diseases. Dr. Price’s research career officially began in 1959 as she worked at the Cornell University Duck Research Laboratory.

Her Research

While working as a research specialist at the Cornell University Duck Research Laboratory, Dr. Jessie Price “focused on the identification and controlling bacterial diseases in commercial white Pekin ducklings” (Quintard Taylor). All of her hard work and focus lead to her discovery of how to recreate the disease in these ducks and create a vaccine against it.

Pasteurella Anatipestifer and the Vaccine

At this time around “10%-30% of the duckling population was lost in the first 8 weeks of their lives due to disease” (poc2.co.uk), this meant an extreme loss of money in the poultry farming business. Dr. Jessie Price found Pasteurella anatipestifer in the ill ducks she researched which caused the life threatening respiratory issues in the animals. Other symptoms include tremors and discolored diarrhea. Pasteurella anatipestifer is a septicaemic disease, meaning a pre-existing bacterial infection enters the blood stream and is highly transmittable. Dr. Jessie Price began the process of research by obtaining fluid from the duck’s cranium. This fluid was then kept in a glass container and stored in order to be used as a study subject.  “Duck broth” is then stored and examined for experimental culture. This research led to the discovery of the Riemerella Anatipestifer vaccince, one of the many vaccines that derived from this research, which works to prevent R. anatipestifer infection at early stages in the ducks life (when they are most susceptible to infection).

Duck Color Colorful Water - Free photo on Pixabay

Ultimately Dr. Price’s research saved the poultry industry and the hundreds of thousands of dollars lost due to poultry death. She passed away in 2015 and Cornell University includes more information on the disease in the College of Veterinary Medicine.

Therapeutics: Can they really beat COVID-19?

As the SARS-CoV-2 virus (which causes COVID-19) struck the world beginning  in early February of 2020, scientists are struggling to find new ways to combat such a violent and airborne virus. As scientist all over the world race to find a vaccine for this virus, others are studying to find new therapeutics to combat and minimize the effects. A team of researchers at University of Georgia have successfully demonstrated that a set of “drug-like small molecules can block the activity of a key SARS-CoV-2 protein — providing a promising path for new COVID-19 therapeutics”. The team of researchers from UGA were the first to evaluate the SARS-CoV-2  protein PLpro, which is an essential part of the coronavirus’s  replication and ability to suppress host immune function. Scott Pegan, director of UGA’s Center for Drug Discovery, collaborated with scientists David Crich, Ralph Tripp, and Brian Cummings to explore inhibitors designed to “knock out PLpro and stop the replication of the virus”.

The Study

Throughout the study, the researchers from UGA began to test a series of compounds that were discovered twelve years ago that were shown to be effective against the SARS outbreak of 2002-03. The COVID-19 pandemic has affected more lives than the SARS outbreak of 2002-03, but at the time when this test was conducted, the researchers believed that the COVID-19 mortality rate was lower based on available numbers in early June. Pegan, along with the other two researchers responsible for this discovery, realized the similarities both SARS viruses possessed and formulated compounds that helped block the proteins of the coronavirus that are responsible for the genes to replicate. These compounds, known as naphthalene-based PLpro inhibitors, are shown to effectively halt SARS-CoV-2 PLpro ability to replicate and suppress host immune functions. “The kind of small molecules that we’re developing are some of the first that are specifically designed for this coronavirus protease……Our hope is that we can turn this into a starting point for creating a drug that we can get in front of the Food and Drug Administration”, Pegan states. UGA students also brought their expertises to the table, trying to compare both SARS diseases in order to find a possible Therapeutic that is affective against COVID-19.

Why is this Important?

As COVID-19 became the most prevalent topic of discussion in 2020, researchers and scientists still don’t know half of the characteristics that trigger the SARS-CoV-2 virus that make it so contagious and harmful. Pegan, along with his associates from UGA, have added to the efforts around the world in learning how to combat this world threatening epidemic. “Pegan’s lab used modeling techniques to locate the differences between PLpro in the 2003 outbreak and the current outbreak, revealing the comparative weakness of the SARS-CoV-2 PLpro and suggesting potential inhibitors for testing”. As many scientists and researchers are struggling to find ways to combat this disease, the discovery of a new compound that can halt the ability for the virus to spread provides hope to finding a cure for this deadly virus.

“Enveloped” viruses, such as SARS-CoV-2, are surrounded by a phospholipid bilayer derived from the host cell as it leaves the cell. This phospholipid contains spike proteins, which is what the virus uses to bind with receptors throughout human cells. The receptor that the virus binds to are known as “Angiotensin converting enzyme 2” (ACE2). After the virus binds with a receptor, it enter the cell via endocytosis, and continues to transfer throughout the cell until it reaches the nucleus, where it’s able to alter the transcription of the RNA within the nucleus and cause more of the virus to duplicate. Vaccines and some therapeutics bind with these spike proteins located around the phospholipid bilayer in order to prevent the proteins from binding to any human cell receptors. 

With the infection and death rate rising each day, along with new discoveries about how this virus functions, it is apparent that scientists and researchers are working as fast as they can to find new therapeutics and vaccines in order to stop the spread of this virus. I believe we all need to put fourth an effort in stopping the spread of this worldwide pandemic, as Scott Pegan did with his courageous findings of a possible new therapeutic, because if we don’t act soon, it will be too late. What do you think? Leave a comment below!

Gut Microbes Help to Advance Flu Vaccines

Beneficial Gut Bacteria

This September, a potentially monumental study was published in the scientific journal, Cell, reporting that researchers have confirmed that microbes present in the gut can change, lower, or jumpstart our immune response.  Previously research has only been done with other mammals such as mice, and this was the first study that linked the results to human subjects. Since most previous trials were conducted on other animals, researchers such as Dan Littman who studies microbiota at NYU School Of Medicine, emphasized there are likely to be large differences in the results for humans versus other animals.   

Specifically, researchers found that people who have not received a flu shot or had the flu within the past 3 years and then were administered broad spectrum antibiotics, produced lower levels of antibodies to the influenza virus. Those subjects who did not receive the antibiotics produced more antibodies to the flu virus. This publication is so noteworthy because previously so little actual human clinical trials were performed to understand the role of the human gut microbiome and its relationship to the strength of our immune response.  

Previous research on how the flu vaccine works and its varying efficiency among many people has been done.  In 2011, Bali Pulendran, an immunologist at Stanford University, found that increased activity in the gene receptor that recognizes the bacterial protein flagellin, the core part flagella, seemed to stand out as the one major change among how well the flu shot was working in varying groups of people.  This underscores the connection between the immune system’s recognition of bacteria (especially gut microbes) and  how well people may respond to the flu vaccine.  

In 2014, this research was followed by gene knockouts being given to mice for the receptor for bacterial flagellin in the flu shot.  The results showed that the mice who received the knockouts made were antibodies than the control mice in the trial.  The researchers suspected this reduction was controlled by the absence or presence of gut microbes and their ability to sense flagellin.  To confirm this, researchers followed up with separate trial in which mice’s microbiota were reduced by the administration of antibiotics before receiving the flu vaccine and control mice who did not receive the antibiotics so their microbiomes remained present.  The results again showed a link that gut microbiota play a role in levels of antibodies produced against their flu shot.  Because of these results, it seemed obvious to test the same situation with humans. 

The current study did just that and was designed as a Phase 1 clinical trial to determine if gut microbes are connected to the efficiency of flu vaccine immunity.   11 adults received broad spectrum antibiotics for 5 days and 11 served as the control and did not receive antibodies.  All subjects receive the influenza vaccine on day 4. The people who received the antibiotics had reduced levels of gut microbes.  However, no major difference was observed in response to the vaccine. These results prompted researchers to dig deeper and they next investigated people who had not had the flu shot or suffered from the flu virus within the last 3 years.  They wanted subjects that would be relatively clear of flu antibodies to begin with. They repeat a very similar study with 11 people, 5 receiving the antibiotics and 6 serving as controls. Everyone got the flu vaccine, but this time the results showed a marked difference in vaccine induced immunity.  Subjects who received antibiotics and had fewer microbes presents, made far fewer flu-specific antibodies.   

This research is very promising not only in the field of flu vaccination, but could reveal that changes to microbiota can have profound impacts on future vaccine development for a variety of pathogens.  Because the results were so tiring, Pulendran is continuing to research deeper into the relationship between gut bacteria and vaccines, for viruses that may affect us in the future. This holds promise for development of vaccines for a wide range of pathogens that attack the human race.  

 

Vaccines for Cancer?

We all know that Cancer is a genetic disease that really can’t be cured, but what if we could develop a Vaccine, like one for a virus, that would target the cells around it to target the cancer? That’s what Professor Darrell Irvine at MIT and his students are trying to accomplish. 

Professor Irvine is working on a vaccine that boosts T-Cells, which is a lymphocyte created in the Thymus along with Epithelial cells to boost immune response. The technique is called CAR-T Cell therapy, and it works by boosting anti-tumor T Cell populations, and using these enhanced populations to fight solid tumors. Before Dr. Irvine’s work, the therapy was unable to target any type of cancer that wasn’t Leukemia. The therapy had a difficult time working on solid tumors because they would attach the T cells to an antigen on the surface of B cells, but the immunosuppressive environment created by the tumor would kill the cells before they could reach the tumor.

But, the researchers at MIT decided to give a vaccine to the lymph nodes, which are host to an abundance of immune cells, instead. Dr. Irvine’s hypothesis was that attaching them to the lymph nodes rather than B cells would give them the proper priming cues to prevent them from dying when they reached the tumor, and he was right. To actually get the vaccine to the lymph nodes the researchers used a technique MIT had developed a few years prior where they attach the vaccine to a lipid tail, which would then bond with albumin, a protein found in the bloodstream, and would then get an uber straight to the lymph nodes. In research in mice, the vaccine has been shown to drastically increase T cell response, and two weeks after treatment and being given a booster vaccine the CAR-T cells made up nearly 65% of the T cells found in the mice. This boost in T cell population resulted in complete obliteration of breast, melanoma, and glioblastoma tumors in 60% of mice.

This success rate is unlike any other treatment for Cancer currently available, and since it is given in a vaccine, memory T cells will be able to detect tumors in the future and destroy them before they become dangerous, just like how regular vaccines work. Between the success rate and the fact that the vaccine will be able to destroy future tumors, there is nothing really like this around for Cancer treatment, and I’m very excited to see the possibilities this has. And the fact that something like a vaccine, which is only capable to treat viruses, can possibly help fight against a genetic disease is also very intriguing.

Rotavirus Vaccine Leads to Important Human Microbiome Experiment

     The journal Cell Host & Microbe recently published Vanessa Harris’s and her team’s (scientists from the Netherlands) research regarding a rotavirus vaccine. Over 200,000 children each year die from rotavirus. It is the prominent cause of diarrheal death in children. Therefore, this line of research is essential to help ensure the global health of all people, especially children.

      Harris’s study consisted of sixty-three, healthy male adults. They were randomly assigned one of three possible arms (branches of types of antibiotics): a broad spectrum (with vancomycin/ciprofloxacin/metronidazole treatments), a narrow-spectrum (with a vancomycin treatment) or the control with no vaccine. After this treatment, the results of the antibodies were tested by the subjects’ viral shedding. The three treatment arms led to similar antibody levels although there was a small increase in viral shedding with the narrow-spectrum antibiotic. Most importantly there was an overall difference in between the antibiotic-treated groups compared to the control arm, with the antibiotic treatments resulting in higher viral shedding. Their results showed an impact of antibiotics on microbiomes reaction to the vaccine.

      The research team also worked with children in Ghana and Pakistan which found a correlation between immunity to the rotavirus vaccine and the presence of a specific, intestinal bacteria. A vancomycin arm was added to attempt to recreate similar results to the earlier study with the adult men. Because rotavirus is a childhood disease, the main outcome of this second half of the study was that further, more detailed and specific research is necessary.

        I believe that the scientists are correct in saying that more research is necessary in order to support any large conclusion, yet it seems to me that bacteria can clearly alter microbiomes reaction to rotavirus vaccine. In my opinion, whether that is a mostly positive or negative effect must be the next step in the research in order to use this information to help children in developing countries like Ghana. Most important, the fact that “…[Harris’s] team believes that understanding that triangulation between bacteria, virus, and the human immune system has the potential for vaccinology and can lead to important uses of the microbiome”, should be the driving factor behind research into human microbiomes.

https://upload.wikimedia.org/wikipedia/commons/9/9e/Rotavirus_replication.png

What came first, the chicken, the egg, or the allergic reaction?

A new study showed the beneficial effects CRISPR/Cas9 can have on those with allergies… in this case, to chickens! For those who don’t know, CRISPR/Cas9 is a gene-editing tool that is used to target certain parts of DNA and modify, disable or enable them. The tool haScreen Shot 2016-04-11 at 12.45.11 AMs been used all across science to inhibit diseases, fix problems with fetuses, change traits, and now to help genetically modify food. Using CRISPR/Cas9 is different than the current definition of genetically modified, which includes injecting chemicals into the food to maximize the amount or change some part of it. This means we humans are ingesting the chemicals; this has led to many concerns. However, CRISPR/Cas9 uses a different approach.

In this specific example, CRISPR/Cas9 creates knockout chickens, or chickens that have had their genes “knocked out”, turned off. Specifically, the ovalbumin (OVA) and the ovomucoid (OVM) genes.  These genes code for proteins that are found in egg whites. It has been discovered that many people are allergic to the proteins produced, so CRISPR/Cas9 targets the genes and turns them off and no proteins are produced. These “genetically modified” eggs are the same as regular eggs just hypoallergenic. In addition, some vaccines are made with egg whites, CRISPR/Cas9 will make it possible for the people who usually have an immune response to the egg whites in those vaccines, to safely receive them. One of the most notable vaccines that uses egg whites is influenza, a very popular vaccine that most of the population receives, and those who couldn’t were at a disadvantage before CRISPR/Cas9. The scientists have said they will continue to cross the modified chickens to see if they are able to knockout more common allergens. So no matter if the chicken or the egg came first, they are now both safe to consume by humans.

 

Can Cats Help Fight AIDS?

Cat

Cats can in fact, unfortunately, get AIDS as well.  Their version of the HIV virus, FIV, is quite similar to the HIV virus. FIV and HIV are the same shape and have the same contents. This new discovery in cats may lead to new discoveries with anti-HIV drugs.

In an article titled “Cats lend a helping paw in search for anti-HIV drugs”, the American Technion Society explains how studying FIV can help scientists discover anti-HIV drugs. FIV and HIV use a protein, integrase, which puts the virus’ DNA into an infected cell’s DNA. Scientists and Professors can now study the Feline FIV virus and its interactions with integrase within cats to figure out important reasons how this deadly protein works. Through studying FIV and integrase, an amino acid change was found that tells us how integrase builds in its primary stages. Now those scientists know about this early assembly process, and can further learn how to terminate this process all together. About 40-45% of the proteins on the amino acid level are the same between FIV and HIV, allowing them to use this discovery on the human counterpart.

The feline virus, FIV, is a lot easier to study and researchers have already found a simpler form (than its HIV counterpart). By studying their 3-D model, they found that integrase’s simple and complex backbones are almost identical. These near identical backbones allow a much easier research path in FIV that will assist similarly with HIV integrase research.

HIV_attachment

 

Image of HIV Virus working

 

FIV and HIV are almost the same in how they work, but the more simple research on the feline version of the virus and integrase will greatly help the fight against AIDS. Who would’ve thought that cats could help fight such a deadly virus?!

 

More Information:

https://www.scripps.edu/newsandviews/e_20030414/elder.html

 

Pics:

http://commons.wikimedia.org/wiki/File:Cat_Cute.JPG

http://en.wikipedia.org/wiki/CCR5_receptor_antagonist#mediaviewer/File:HIV_attachment.gif

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