Vaccine development

22 I Biology Vaccine Development From the lab bench to the doctor’s office

BY CAILEY DENONCOURT, BIOENGINEERING, 2022

The race to develop a vaccine for the ongoing COVID-19

pandemic spans across the world as the virus continues

to take thousands of lives every day. Unfortunately, the fastest vaccines typically take at least five years to fully develop; this includes multiple failed attempts before commercializing an effective vaccine that successfully passes all clinical trials and safety guidelines. As businesses start to reopen across the country and social distancing guidelines continue to be ignored, infection rates coming into Fourth of July weekend are at an all time high. With another wave expected later this year, the rapid development of a vaccine could save thousands of lives.

In order to fully understand the lengthy vaccine development process, how the vaccine is able to give an individual immunity to the virus must also be understood. Vaccines are developed in order to mimic the agents of the virus, so that the immune system can build a defense system without directly experiencing the negative symptoms associated with infection.

When the virus first enters the body, an antigen presenting cell (APC) breaks down the virus and displays the antigens on its surface, which are detected by T-helper cells to alert an immune response. This response recruits two types of B cells: plasma and memory cells. Plasma B cells are antibody factories. The produced antibodies can then attach to the antigens on the virus prohibiting it from entering the cells. More critical are memory B cells, which memorize how to produce these antibodies, so the immune system can respond stronger and swifter if ever exposed to the virus again.

Starting in the lab, the traditional vaccine development process begins with isolation of the virus from an affected individual, which is then grown in bioreactors and harvested for modifications. These modifications can range widely based on the virus and can include weakening, inactivating, or removing a portion of the virus so that an immune response is still activated with no symptoms.

Since a vaccine requires injecting parts or the entire virus into the patient, there are multiple safety guidelines that are regulated by the Center for Biologics Evaluation and Research. Once a vaccine candidate has been developed, it undergoes a series of preclinical trials, which must prove its effectiveness and safety before moving onto clinical trials. The three stages of clinical trials allow the companies to evaluate the safety and effectiveness directly in humans, while also determining the correct dosage and possible side effects. On top of ensuring the vaccine is safe and effective, manufacturing development is equally important in order to ensure that the commercialization of the vaccine is able to support distribution to a large population.

DESIGN BY SOPHIA HITT, BIOLOGY, 2023

This is a very extensive, time-consuming process that would take extremely long to complete during the current pandemic. Thus, during an outbreak, this timeline is often accelerated by overlapping the pre-clinical, clinical, and manufacturing phases. During a public health emergency, the FDA is allowed to authorize emergency-use potentially before all the usual bars have been met. This, combined with compressing the timeline, is leaving the public with many reservations. Even with the possibility of record breaking release, as companies continue to push the regulation limits, the vaccine may not be as widely accepted or effective as needed to stop the spread.

As of early April 2020, there are about 115 vaccine candidates in development across the globe. The most advanced candidate being the mRNA-1273 from Moderna, which was developed at a record pace of 42 days. This was possible with a newer variety of vaccines that do not involve directly injecting the virus into the patients. Similarly to the traditional process, the virus is isolated from an infected individual. However, instead of direct injection, Moderna uses mRNA. It encodes for the instructions on how to make the spike protein, a necessary agent of the COVID-19 virus that allows it to invade cells. The mRNA is taken in by APCs in the immune system, and they are able to directly use the mRNA to produce the protein with the components they’re already equipped with. The development of RNA vaccines are becoming more common because of shorter manufacturing times and easier antigen manipulation, so although no mRNA vaccines are available to date, their popularity is expected to increase in the future.

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Nature (2020). DOI: 10.1038/d41573-020-00073-5 The New England Journal of Meadicine (2020). DOI: 10.1056/ NEJMp2005630 PHOTO BY KEVIN KOBSIC VIA FLICKR

Th e role of m uci ns i n disease transmission

BY RYAN BRADY, CHEMICAL ENGINEERING & BIOCHEMISTRY, 2022 DESIGN BY KATIE GREEN, BIOENGINEERING, 2022

The body is a well-designed system

with a variety of barriers to keep

invaders out. These range from the physical barriers of the skin to the biological protection of the immune system. However, the structures of the face such as the eyes, nose, and mouth represent major vulnerabilities. The nose and mouth are an interconnected system in which saliva and mucus serve as the physical barriers to keep viruses and other contaminants out. Coughing and sneezing are effective means of keeping viruses and other foreign material out of the body by expelling these invaders into the environment. These expulsions create small particles of liquid which travel through the air, potentially infecting others with the virus.

One MIT study was conducted this year and demonstrated the potential impact of coughing and sneezing on disease transmission. The researchers generated a number of visualizations of the small liquid particles that are generated. These visualizations show that the particles gathered in clouds up to 27 feet from the original expulsion. Physical barriers such as masks can help to minimize the size of the emulsions and decrease the potential for viral transfer. This demonstrates the need for masks in public and the need for social distancing to prevent the direct transfer of these particles. However, another means of transmission is the deposition of these droplets onto surfaces. The analog to this MIT study is an early publication in The New England Journal of Medicine from earlier in 2020, which attempted to assess the survivability of the aerosolized virus on surfaces. It identified that the virus could potentially survive up to 72 hours on plastics and stainless steel. However both this and the MIT study represent preliminary findings which fail to fully capture the phenomena occurring. Both studies simplified the chemistry of these droplets to aqueous solutions. In reality, these droplets contain a number of biochemical compounds and cells which could potentially impact the survivability of the virus. One of the compounds that directly interacts with the virus are mucins.

Mucins are a specialized type of protein designed to form chemical barriers in epithelial tissues. There are up to 20 different types, but all of them fall into the class of glycoproteins. Glycoproteins consist of proteins that are covalently linked to carbohydrates. For mucins, the proteins serve as a sort of a molecular backbone, off of which numerous carbohydrates are linked. These carbohydrates form chains off of the protein to create a matrix of said chains. This matrix provides the functional relevance of these molecules, allowing large molecules to get stuck within it. These proteins can be either membrane-bound or secreted out of cells to form a gel layer. This gel layer is part of t h e epithelial lining. As part of the lining it will be present in the throat and nasal cavities and can therefore be expelled as part of a sneeze or cough.

One particular mucin is present in high proportions in the mouth: MUC5B. This mucin is most likely to be present in the particles expelled via coughing and sneezing. It has been shown to decrease the amount of bacteria and fungal infections in that area. This is related to the spread of diseases because the particles expelled from the body contain these mucins, which can impact the survivability of particles TO READ THE FULL ARTICLE, VISIT NUSCIMAG.COM

outside the body.