Vaccines Versus Viruses
Virus components
Biological viruses are a curious entity as they still spark debate among scientists about whether or not they are alive. The generally agreed upon biological characteristics of determining whether something is alive focuses on its ability to reproduce and to metabolize (use energy). A virus can do both of these, but it must be inside a cell and use the cell’s molecular machinery in order to do so. It is essentially genetic material (DNA or RNA), that is wrapped up in some proteins that allow it to infiltrate cells. Here is an excellent article published by the Microbiology Society, illustrating both sides of the argument of whether or not viruses are alive.
To emphasize how few components a virus is made up of, we can compare it to a single sperm, whose sole purpose is to transport genetic material to an egg. Like a virus, sperm contains genetic material, although normally only half of what is required to create life in order to complimentary fertilize the egg. This genetic material, enclosed in a “head” called an acrosome, contains some really funky enzymes that enable the sperm to break through the tough outer layer of the egg in order to fertilize it. Sperm also has a tail to help it swim, and the ability to make its own energy molecules (ATP). Viruses do not even have the ability to make their own energy! Although their overall structure seems simple, this simplicity actually makes viruses exceptionally resilient and challenging to target. Instead of relying on a variety of different components, it essentially has two: its genetic material (either DNA or RNA, depending on the virus) and its protein casing (capsid). Some viruses can even commandeer the cellular membrane of its host, creating an envelope to disguise itself. When an organism is more complex, there are more crucial components to try to target in order to disable it. For example, bacteria have their own unique molecular machinery to replicate themselves, cell membranes, protein replication processes, DNA, and additional components that allow them to perform whatever their function happens to be. This provides many different targets that scientists can use to develop antibacterial medication. In fact, there are more than 15 different classes of antibiotics, as they provide many more options for targets than viruses1. Once we move into macroscopic organisms, such as humans, there are exponentially more vulnerabilities to consider, including susceptibility to viruses - which have not yet been observed to be vulnerable to each other.
Viruses can cause infections as a result of their replication process. In order for our bodies to fight an infection, it has to recognize that there is an infection in the first place. All cells have markers that identify themselves to each other and to other cells. A great example of this are blood types, where different markers on the outside of red blood cells identify whether blood is A-, B-, AB-, or O-type. O-type blood has no markers, A has one type of marker, B has a different type of marker, and AB has both markers. The body is able to identify that a blood type is compatible by whether these markers are present. If a marker is absent, the body cannot identify it, but if the marker is present, the body can identify it. This is why O blood is the universal donor, because there is nothing to make it stand out, and AB is the university recipient, because the body recognizes all the markers. When your body first recognizes an infection, whether bacterial or viral, it tries fighting the infection off. However, aggressive pathogens (viruses, bacteria, etc) can replicate very rapidly causing the infection to be in full force leading to detrimental results. A virus that is able to commandeer its host’s cellular membrane can even disguise itself as part of its host and be trickier to target. Because viruses are relatively simple, they are able to replicate very rapidly, to the point where the number of viruses present, called the viral load, is too high for the body to fight off the infection. The purpose of vaccines is to prepare the body for battle by being able to recognize the intruder earlier before the viral load becomes harmful. Vaccines stimulate the immune system to be on the defense by triggering your body to develop fighting antibodies before an actual viral invasion occurs. There are a few different ways that vaccines can do this:
- Virus vaccines: a weakened or inactivated version of the virus that is developed by growing it in animal or human cells to pick up mutations in its genetic code causing it to weaken. Viruses can also be inactivated using chemicals or heat. Vaccines against measles and polio are weak/inactivated virus vaccines.
- Viral-vector vaccines: these vaccines behave like a virus, in that they infect cells to replicate their DNA inside them. However, they are precisely genetically modified to carry DNA into cells to produce proteins that fight off disease-causing viruses. They are essentially a viral “infection” that causes cells to produce antibodies required to fight harmful viruses. In essence, in the battle of vaccine versus virus, viral-vector vaccines are viruses that have “switched sides”. The cool thing about this approach is that they are customizable. Scientists are testing these vaccines to determine whether they are able to target different strains of the same disease using a multi-pathogen/polyvalent viral vector vaccine. There is also the potential to stimulate immunity for different diseases by modifying the viral-vector to target different infections, called a multi-pathogen viral vector vaccine2.
- Nucleic acid vaccines: These types of vaccines are made up of either DNA or RNA, the genetic material (nucleic acids) of living organisms... and viruses. The idea is that the genetic information within both virus vaccines and viral-vector vaccines is all that is needed to stimulate an immune reaction to prepare the body for battle. Although these have been deemed safer and easier to develop experimentally, they are currently an unproven technology.
- Protein-based vaccines: The vaccines previously mentioned have focused on using genetic material, but there is the other viral component that can be targeted - the capsid! Protein-based vaccine technology uses the protein coating of the virus to stimulate an immune response. It’s an “empty-shell” approach where the proteins forming the outside of the vaccine are used, but there’s no genetic material within to actually allow the virus to replicate. These are a little trickier to produce, however hepatitis B vaccines use this technique3.
Here is an excellent article, complete with visual flowcharts, explaining how these different types of vaccines that could be developed for SARS-CoV-2 here.
The purpose of vaccines is to target infections from microorganisms, such as bacteria and viruses. These microorganisms are abundant, in fact there are an estimated 1031 virus particles just floating around in the ocean6. That’s a lot of pressure on our bodies to be able to tackle the diversity of potential infections out there. Our body creates antibodies in order to handle this diversity, a protein that has one heavy chain binding to two light chains. This allows for a significant flexibility in mixing and matching the heavy and light chains to target the exorbitant amount of unwelcome guests that can cause disease or complications in our bodies. In fact, biotechnology uses this diversity as a targeted treatment and is a rapidly growing field of medicine. Until recently, it was thought that all antibodies had a similar structure which has been tricky in targeting SARS-CoV-2 as a result of the large antibody size. Fortunately, LLAMAS have come to the rescue! Yes, llamas. Members of the camel family, (Camelidae – that’s right, llamas are part of the camel family), have a unique set of antibodies that contain only the heavy chain component, and are thus smaller4. They are still able to bind to antigens, and theoretically can be easier to produce in a laboratory environment using bacteria or yeast cells. This is possible because of their decreased complexity compared to regular antibodies that have multiple types of chains. In fact, scientists have tested these single domain large-chain antibodies against SARS-CoV-2 by immunizing a healthy, happy, llama named Winter, and found that she was able to produce antibodies that effectively bound to and neutralized the SARS-CoV-25. For an excellent video explaining this research more extensively, published by the well-researched YouTube channel SciShow, click here.
The vast diversity that makes biology so wonderfully fascinating is what makes it exceptionally complicated when developing ways to fight infections. This diversity makes it much trickier to treat diseases using only one method, but if we can prepare our body ahead of time with vaccines, our body has a better chance of fighting it off. Vaccines give our bodies an immune boost to prepare us against a viral invasion. Even recognizing parts of a virus and stimulating an immune response is crucial as viruses can evolve much more rapidly than we can. With their significant evolutionary advantage, it is not always possible to fight them off on our own. Without vaccines, there would be millions of deaths, especially among children, as a result of polio, tetanus, hepatitis B, hepatitis A, rubella, HiB, measles, whooping cough, pneumococcal disease, rotavirus, mumps, chickenpox, diphtheria, tuberculosis, meningococcal disease, cholera, rabies, and encephalitis. Thanks to scientific ingenuity, we have a way to prepare ourselves for viral battle!
References/Other Information
Werth BJ. Overview of antibiotics. Merck Manual 2018.
Lauer KB, et al. Multivalent and multipathogen viral vector vaccines". Clinical and Vaccine Immunology 2017; 24(1): e00298-e00316.
Protein-Based Vaccine . ScienceDirect: Topics.
Conrath KE, et al. Emergence and evolution of functional heavy-chain antibodies in Camelidae . Development & Comparative Immunology 2003; 27(2): 87-103.
Wrapp D, et al. Structural basis for potent neutralization of betacoronaviruses by single-domain camelid antibodies . Cell 2020; 181: 1-12.
Brown N & Bhella D. Are Viruses Alive? Microbiology Society May 2016.