BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: #Covid-19Vaccine

How is Omicron still a problem?

Covid-19 under a microscope

 

Allow me to take you back to the early days of the Covid-19 pandemic. Alpha, and Delta were the primary variants.

And then Omicron stumbled in, and unlike the others, never left.

Unlike the others, who had viciously ensnared others to their deaths, Omicron was more akin to a hard cold, or the flu. Whilst it shared flagship symptoms like parosmia (loss of smell/taste) and other respiratory symptoms, they resulted in less hospitalizations. In addition, we were going stir crazy and had started to unlock the lockdown. 

And Omicron, unlike the others, was a rapidly evolving virus, one variant one second and another the next. The rapid mutations in the epitopes (the spike protein that the immune system uses to distinguish it from other viruses) made vaccines, which are designed to emulate the epitopes so the body can recognize it (hence the potential fever- your body is learning the epitope’s shape so it can catch the real thing faster), next to impossible to settle on. Trying to get a working vaccine for it was like trying to hold a tiny fish in the rain- it just kept slipping away. 

And now again, descendants of Omicron are dominant again.

HV.1 is a descendant of Eris (EG.5) but isn’t really that different from Eris. Vaccines that are designed to target XBB (another offshoot) still work on both of them. HV.1 is only dominant for minor mutations, as vaccines still work.

The real worry is BA.2.86, which has been determined to evade the immune system. It, in comparison to say, EG.5.1 or XBB.1.5, resulted in a lower concentration of neutralizing antibodies, meaning one infected would be infected for longer.

Its descendant, JN.1 might be even better at it. It can be transmitted at low levels due to its highly mutated spike protein, and still evades the humoral response more effectively than its predecessor.

I, for one, think that Omicron isn’t going away. It mutates too quickly to truly be caught. But I think a monovalent vaccine is possible per each set of dominant strains. And to that, I mean it will likely become another vaccine to get annually in the fall.

Unveiling the Nobel-Worthy Breakthrough: The mRNA Pioneers Behind Life-Saving Vaccines

 

Solo-mrna-vaccine-3

In a historic announcement, the Nobel Prize in Physiology or Medicine for 2023 has been awarded to biochemist Katalin Karikó and Drew Weissman, recognizing their groundbreaking contributions to mRNA research. Their work laid the foundation for what has become one of the most influential medical advancements of our time: the development of mRNA vaccines against COVID-19.

Karikó, currently at the University of Szeged in Hungary, and Weissman from the University of Pennsylvania, received this prestigious honor for their pioneering research on modifying mRNA. These modifications were crucial in making the first COVID-19 vaccines possible, notably those produced by Pfizer/BioNTech and Moderna.

Revolutionizing Vaccines

Traditional vaccines typically use weakened or killed viruses, bacteria, or proteins from pathogens to stimulate the immune system. However, mRNA vaccines work differently. They contain genetic instructions for building viral proteins. When administered, these instructions prompt cells to temporarily produce the viral protein, triggering an immune response. The immune system then builds defenses, providing protection if the person is later exposed to the actual virus. This may sound familiar, as AP Bio has taught about immune response and cells. We learned that memory T cells are a crucial component of the immune system, formed after the body encounters a pathogen like a virus or bacteria. These specialized cells “remember” the specific characteristics of the invader, allowing for a rapid and targeted response upon subsequent exposures, effectively combating and neutralizing the illness. Memory B cells, a crucial component of the adaptive immune system, exhibit remarkable specificity and functionality. During the primary immune response, these cells undergo affinity maturation, producing high-affinity antibodies with increased binding capacity to pathogen-specific antigens. Notably long-lived, memory B cells persist in the body, ensuring prolonged immunity. Upon re-exposure, they swiftly differentiate into Plasma B cells, which serve as antibody factories, producing copious amounts of antibodies tailored to the familiar pathogen. On the other hand, memory T cells, including cytotoxic and helper T cells, play distinct yet coordinated roles. Cytotoxic T cells retain the capacity to directly eliminate infected cells, preventing pathogen spread, while helper T cells release cytokines that stimulate antibody production by B cells and enhance cytotoxic T cell activity. With immunological memory, memory T cells provide rapid and targeted responses upon reinfection, actively surveilling for cells displaying specific antigens associated with previously encountered pathogens. Together, these memory cells form a sophisticated and enduring defense mechanism, contributing to the immune system’s ability to combat and neutralize pathogens efficiently.

The technology behind mRNA vaccines has proven immensely effective in combating the COVID-19 pandemic. As of September 2023, over 13.5 billion COVID-19 vaccine doses, including mRNA vaccines and other types, have been administered globally. These vaccines are estimated to have saved nearly 20 million lives worldwide in the year following their introduction.

Modified mRNA and Its Potential

RNA, the lesser-known cousin of DNA, serves as the genetic instruction manual for cells. Messenger RNA (mRNA) copies genetic instructions from DNA and is crucial for protein synthesis. Karikó and Weissman’s pivotal contribution was modifying mRNA building blocks to overcome challenges in early trials.

Traditional mRNA injection would trigger adverse immune reactions, leading to inflammation. By swapping the RNA building block uridine for modified versions, the researchers found a solution. Pseudouridine and later N1-methylpseudouridine proved effective in dampening harmful immune responses. This breakthrough, dating back to 2005, enabled the safe delivery of mRNA to cells.

“The messenger RNA has to hide and go unnoticed by our bodies,” explains Kizzmekia Corbett-Helaire, a viral immunologist at the Harvard T. H. Chan School of Public Health. The modifications developed by Karikó and Weissman were fundamental, allowing mRNA therapeutics to hide while being beneficial to the body.

This technology extends beyond COVID-19, with potential applications against other infectious diseases, cancer, and even rare genetic disorders. Clinical trials are underway for these applications, though results may take several years to emerge.

A Journey Decades in the Making

The road to this groundbreaking achievement was not without obstacles. In 1997, Karikó and Weissman, working in separate buildings, collaborated to address a fundamental problem that could have derailed mRNA vaccines. Initial setbacks, including failed clinical trials in the early 90’s, led many researchers to abandon mRNA as a viable therapeutic approach.

Undeterred, Karikó and Weissman persisted. “We would sit together in 1997 and talk about all the things that we thought RNA could do,” Weissman reflected. The duo’s resilience led to the formation of RNARx in 2006, a company dedicated to developing mRNA-based treatments and vaccines.

Despite the groundbreaking nature of their work, Karikó’s contributions were initially overlooked. Ten years ago, she faced termination from her job and had to move to Germany without her family to secure another position. The Nobel recognition sheds light on her unwavering commitment to mRNA therapeutics.

The Nobel Committee’s decision to acknowledge this achievement swiftly, a mere three years after the vaccines demonstrated their medical importance, highlights the urgency and impact of mRNA technology. Emmanuelle Charpentier and Jennifer Doudna’s Nobel Prize for Chemistry in 2020, awarded eight years after the description of CRISPR/Cas 9, reflects a similar trend of more current acknowledgments.

In a press conference at the University of Pennsylvania, Weissman expressed his surprise at the recognition. “I never expected in my entire life to get the Nobel Prize,” he confessed. The laureates will share the prize of 11 million Swedish kronor, approximately $1 million.

A Nobel-Worthy Legacy and a Glimpse into the Future

The timely recognition of Katalin Karikó and Drew Weissman emphasizes the transformative potential of mRNA therapeutics, extending far beyond the current success against COVID-19. As we celebrate this Nobel-worthy legacy, it opens a new chapter in medical science, offering hope for innovative solutions to combat various diseases and improve human health.

The journey from a meeting in 1997 to the global impact of mRNA vaccines in 2023 showcases the power of perseverance, collaboration, and the pursuit of groundbreaking ideas. 

What do you think about mRNA vaccines? Did/Will you receive one?



Clot Chronicles: Decoding the Intricacies of Proteins and Vaccines in COVID-19 Immunity

Are you vaccinated for COVID-19? Well, the article titled, Protein interaction causing rare but deadly vaccine-related clotting found, discusses a mechanism that has led people to deadly clots. These scientists identified that some individuals developed these clots after receiving certain COVID-19 vaccines. The research explains  Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT) which is a condition where the body produces blood clots. When a patient has this condition antibodies attach to a protein called Platelet Factor 4 (PF4), forming immune complexes. 

Protein PF4 PDB 1f9q(PF4)

Additionally, Platelet Factor 4 is a small cytokine in the CXC Chemokine family. Cytokines are small proteins that are released by macrophages to attack a virus.  Platelet Factor 4’s most prominent function is to promote blood coagulation; but, it is also involved in innate and adaptive immunity

The Immune System, as discussed in depth in my AP Biology class,  protects the body against pathogens such as bacteria and viruses. COVID-19 is an example of one of these viruses that infects the body through its various openings, most generally, the nose and mouth. Innate and Adaptive response are the two parts of the immune system. The innate response is something everyone is born with, works immediately upon infection, and is nonspecific which contrasts the adaptive immune response which is slower and more targeted. 

Returning to the vaccines, these complexes activate platelets and immune cells and lead to clotting and inflammation. Inflammatory responses are a result of the mast cells locating the “invader” and releasing histamine as an “alarm” to the body. Histamine causes inflammation in the body and an inflammatory response which is typically painful. When I had COVID I remember taking anti-inflammatory medications to reduce the pain I felt from the inflammatory response I was experiencing such as my high fever.

In summary, the ongoing research wants to find people who might be more likely to get VITT with future vaccines, so we can understand and manage the risks better, making vaccines more effective. 

After reading this article and doing outside research I believe this study to be highly important because researchers understand how to make vaccines safer for the future. As someone who has not been vaccinated it is valuable for me to know the risks and rewards of the vaccine. So … COVID-19 vax worth it or not? Let me know what you think in the comments!

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