BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: vaccines

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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