BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: influenza

“4′-FlU” – The Future of Flu Fighting!

This study conducted by researchers at Georgia State University’s Center for Translational Antiviral Research examined the effectiveness of a new potential antiviral drug, 4′-fluorouridine (4′-FlU), against influenza A viruses. Research had shown promise for 4′-FlU in combating different strains of influenza, including seasonal and pandemic viruses, in cell cultures and animal models.
The researchers investigated whether influenza viruses could develop resistance to 4′-FlU and the impact of such resistance on the virus’s ability to spread. They found that while some influenza strains developed resistance to the drug, these resistant variants were significantly weakened in animals, particularly in their ability to cause severe respiratory infections and transmit between hosts.

SARS-CoV-2 virion animation

In connection to our class, the concept of natural selection, which is a fundamental principle in evolutionary biology, is evident in the development of resistance to 4′-FlU by the influenza viruses. Through the process of random mutations shown by the drug, resistant variants of the virus emerge, highlighting the role of genetic variation in evolutionary processes. Secondly, the study underscores the importance of understanding molecular genetics, specifically the structure and function of DNA and RNA. The identification of specific genetic mutations in the influenza virus that create resistance to 4′-FlU demonstrates how changes in nucleotide sequences can lead to altered genetic characteristics, such as drug resistance. The study identified specific genetic mutations in the influenza virus that became resistance to 4′-FlU, but the researchers determined that these mutations were unlikely to have significant clinical implications. They also discovered that administering 4′-FlU at certain doses could effectively overcome moderate resistance and prevent lethal infection in mice.

Influenza Virus - 52461389748
The study shows the urgent need for new influenza therapeutics, given the limitations of current antiviral drugs, which often face challenges with viral resistance. The research provides valuable insights into the development and potential effectiveness of 4′-FlU as a treatment option for influenza, suggesting hope for improved battle against future influenza outbreaks or pandemics.

 

(Post includes edits suggested by Grammarly) 

Fighting the Flu: Why Kids Need More Influenza Antivirals

Influenza Virus

Influenza, otherwise known as the flu, is a very well known disease, that is unfortunately still very common. Given its commonality, there are many different ways to try and treat or mitigate the virus. Despite this fact, we can see discrepancies between guidelines and actual prescription practices for flu treatment among children, thanks to the study “Trends in Outpatient Influenza Antiviral Use Among Children and Adolescents in the United States.” 

The lead author, James Antoon, a professor and doctor at Vanderbilt, emphasizes that antiviral treatment, especially when administered early, significantly improves health outcomes in influenza cases among children. However, the study reveals that a significant proportion of children, particularly those under the age of 5 and especially those under 2, are not receiving the recommended antiviral treatments. In fact, only about 40% of children studied were treated with antivirals, despite guidelines suggesting that all of them should receive this treatment.

Interestingly, the study reveals a notable disparity in the geographic use of influenza antivirals, showing a significant difference in prescription rates across different regions, independent of flu cases.

The reasons behind the under prescription of antivirals in children is likely due to various factors, including differing perceptions about effectiveness, variations in the interpretation of diagnostic testing, misunderstanding of national guidelines, and concerns about potential adverse drug events associated with certain antivirals, such as oseltamivir.

Additionally, the study mentions a previous investigation led by Antoon that explored neuropsychiatric side effects in children diagnosed with influenza. While these events are relatively infrequent, the study observed that they occurred in both treated and untreated children.

The research emphasizes the importance of improving flu management among vulnerable children in the United States, highlighting the need for better following of guidelines regarding antiviral use in pediatric flu cases.

This study connects to a few things we’ve learned this year in our AP Biology class. The way oseltamivir works, is that once inside, your body metabolizes it, which activates the oseltamivir. Once activated, it binds to and inhibits the active sites of the enzymes responsible for spreading the flu throughout a host’s body. As we learned in AP Biology, it doesn’t completely stop the spread of the virus, but it definitely slows it down, allowing your white blood cells to eradicate the virus.

Do you think the underuse of antiviral medications in children with influenza is a widespread issue? How might this research impact pediatric healthcare practices in managing flu cases more effectively?

(Post Includes suggestions made by ChatGPT)

20 VS. 4- A Universal Flu Vaccine

Flu Shot Advertising

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.

Threat of “Tripledemic” This Year

For the past three years, COVID-19 has been on everyone’s minds. Between the mask-wearing, quarantining, and social distancing performed over this time frame, it is understandable that the spread of other viruses was also curtailed by these measures. However, people are increasingly returning to pre-pandemic activities, and often unmasked – the potential for other viruses to spread rapidly and easily is back.

San Francisco COVID social distancing poster

This winter, influenza is a threat as always – the Centers For Disease Control and Prevention estimate that 2,100-6,200 Americans have already died this year – and fewer Americans have received flu shots this year compared to past pre-pandemic years. but the Respiratory Syncytial Virus (RSV) has the potential to be incredibly deadly this year too.

RSV primarily threatens children and infants, who lack protection with their weaker immune systems. Furthermore, there is currently no vaccine available for RSV. Experts suggest this season to be particularly dangerous because a generation of children have not had frequent exposure to various infections in their lifetime due to the social distancing required by the pandemic, combined with the gradual return of normal activity. When infected, the body’s innate immunity responds. If it fails to stop the virus from spreading, the adaptive immune response begins. Once the infection, in this case RSV, COVID-19, or Influenza are successfully fought off, T-memory cells and B-memory cells continue circulating to prevent serious reinfection. If reinfected, the secondary immune response that occurs will provide better long-term protection.

Children are typically exposed to RSV at least once before the age of two; that number has dropped drastically since the COVID-19 pandemic (not to say that these precautions were not vital and instrumental in controlling the spread of COVID-19). Therefore, they lack this immunity. Unfortunately, there is not much for medical professionals to currently do about this without a vaccine – simply wait for exposure to the virus to rise again. However, the effective vaccines developed for both COVID-19 and Influenza are capable of slowing the spread of both of these viruses – and have been doing so. Through consistent vaccination, we may be able to escape the “tripledemic” experts have been warning of this year.

A Super Self-Assembling Vaccine Booster to the Rescue!

Vaccines: a topic on the forefront of the minds of scientists, researchers, and the general public. With the novel coronavirus and fiery online debates led by coined “anti-vaxers” about the effectiveness and dangers of vaccination, biologists are racing to discover more methods to improve these life-saving injections. An essential component of many vaccines, including ones used to prevent cervical cancer, influenza, and hepatitis is the adjuvant: a “booster” ingredient that helps the vaccine create a longer-lasting, stronger immune response in the patient. Recently, a team of scientists in Japan discovered a new adjuvant—a molecule called cholicamade—that was equally as effective in treating influenza in mice as its predecessor, Alum. The emergence of this new ingredient is exciting, but the real novelty lies in the process these biologists used in discovering chloicamade: looking at molecules that could self-assemble.

What is the self-assembly of a molecule, or multiple molecules? Multiple molecules are said to self-assemble if they are able to organize into a defined pattern without the intervention of an external source, such as heat. These molecules will form ionic or hydrogen bonds with each other, similar to the joining of water molecules, since they don’t share electrons equally, as we learned in AP Biology. Identifying molecular structures that self-assemble is a common practice in materials science, but not often used in researching adjuvants. This team of biologists and chemists hypothesized that utilizing molecules that form in this fashion for disease treatments may be effective because pathogens in viruses also form through self-assembly. They wondered if a similar method in structural formation between a treatment and its virus would trigger a similar immune response.  

And it did! Cholicamide self-assembles through ionic bonds to create a structure which looks almost identical to a virus, triggering the same immune system cells to react. The structure of the molecule

An image of the influenza virus, which the treatment would attempt to replicate.

lends itself to the formation of ionic bonds because of its inherent polarity and electronegative elements. The molecule can be injected directly into vacuoles that will connect it with the specialized receptors which will trigger the appropriate immune response. A vacuole’s ability to store water and other nutrients (as we learned in AP Biology) as well as transport these nutrients throughout an animal cell is vital in ensuring the treatment binds to the correct receptors. Uesugi, a leading scientist in the study, hopes “the new approach paves the way for discovering and designing self-assembling small molecule adjuvants against pathogens, including emerging viruses.” What do you think about this new method in discovering vaccine treatments? How do you see the future of vaccines changing as more adjuvants are researched? I believe there is nothing more exciting than not only confirming the effectiveness of a new treatment, but also conducting the research with a new approach or perspective.

 

 

 

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.  

 

Does Exposure to Toxins In the Environment Affect One’s Offspring’s Immune System?

A study has recently surfaced stating that maternal exposure to industrial pollution may harm the immune system of one’s offspring and that this impairment is then passed from generation to generation, resulting in weak body defenses against viruses.

Paige Lawrence, Ph.D., with the University of Rochester Medical Center’s Department of Environmental Medicine, led the study and conducted research in mice, which have similar immune system functions as humans. Previously, studies have shown that exposure to toxins in the environment can have effects on the respiratory, reproductive, and nervous system function among generations; however, Lawrence’s research is the first study to declare that the immune system is also impacted.

“The old adage ‘you are what you eat’ is a touchstone for many aspects of human health,” said Lawrence. “But in terms of the body’s ability to fights off infections, this study suggests that, to a certain extent, you may also be what your great-grandmother ate.”

“When you are infected or receive a flu vaccine, the immune system ramps up production of specific kinds of white blood cells in response,” said Lawrence. “The larger the response, the larger the army of white blood cells, enhancing the ability of the body to successfully fight off an infection. Having a smaller size army — which we see across multiple generations of mice in this study — means that you’re at risk for not fighting the infection as effectively.”

In the study, researchers exposed pregnant mice to environmentally relevant levels of a chemical called dioxin, which is a common by-product of industrial production and wast incineration, and is also found in some consumer products. These chemicals eventually are consumed by humans as a result of them getting into the food system, mainly found in animal-based food products.

The scientists found the production and function of the mice’s white blood cells was impaired after being infected with the influenza A virus. Researchers observed the immune response in the offspring of the mice whose mothers were exposed to dioxin. Additionally, the immune response was also found in the following generations, as fas as the great-grandchildren (or great- grandmice). It was also found that this immune response was greater in female mice.  This discovery now allows researchers to have more information and evidence to be able to more accurately create a claim about this theory.

As a result of the study, researchers were able to state that the exposure to dioxin alters the transcription of genetic instructions. According to the researchers, the environmental exposure to pollutants does not trigger a genetic mutation. Instead, ones cellular machinery is changed and the immune response is passed down generation to generation. This discovery explains information that was originally unexplainable. It is obviously difficult to just avoid how much toxins you are exposed to in the environment, but it is definitely interesting to see the extent of the immune responses in subsequent generations. We can only hope that this new information, and further discoveries, help people adjust what they release into this world that results in these harmful toxins humans are exposed to, and their offsprings.

 

 

 

Stop! Don’t Smell the Roses!

800px-SneezeDuring the flu season, we all try to be a little more vigilant when it comes to germs. Even as a self-proclaimed “germaphobe,” I was not as lucky to escape the evil grasp of the disease. Aside from recognizing  the obvious perpetrators, who include those who refuse to cover their mouths, people who breathe just a little too close to me, and  grimy freshmen, I wanted to find out a little more about the  origin of diseases.

 An interesting area of research regarding the topic is being pioneered by Scott McArt and Lynn Adler of the University of Massachusetts Amherst. They are investigating how great a role flowers play in the transmission of diseases. Around 190 studies having to do with flowers and diseases they pass on have been dated back to the lat 1940’s. This research is important because it can “help efforts to control economically devastating pollinator-vectored plant pathogens.” Still, this topic is very new and not as conclusive as many would think. Despite this fact, “eight major groups of animal pathogens that are potentially transmitted at flowers” (by bees and other pollinators) have been discovered. It is unknown whether pathogens are transmitted via the chemical or physical traits of flowers. 

The main goal of the study was to attention to the need to further explore the relationship between flowers, their pollinators and diseases, as many people have expressed concern for “the pollinator declines caused in part by pathogens.” Do you agree that this is an area worth researching?

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