Will new tech or old standbys work best for a COVID-19 vaccine?
Successful vaccines are great mimics. For centuries, scientists have been designing them to produce the same effects as a natural infection. As they’ve learned more about how vaccines work for different harmful viruses and bacteria, called pathogens, the technologies used to make them have evolved. Now, scientists are pulling out all the stops, using both new tech and tried-and true options in their quest to stop the novel coronavirus SARS-CoV-2.
Long before what’s known as modern medicine, it was observed that after surviving certain contagious diseases, people seemed to be resistant, or immune, to getting sick from it again. As early as 17th century China, scientists have been trying to replicate the body’s natural response through inoculation with vaccines. In these initial attempts smallpox was prevented by inserting a small amount of a live related virus (cowpox) into a skin tear.
But first — how do vaccines work?
When a person is infected with a pathogen, their body typically responds by making specific antibodies against it. These can be against many different parts of the pathogen, often to proteins on the outside that have sugars attached to them. Many different antibodies are made, varying in how effective they are at blocking, or neutralizing, the infection. This takes some time when someone has never seen that pathogen before. So, the person can get quite sick or even die if they can’t make enough effective antibodies before the bacteria or virus replicates to large numbers.
After the body successfully fights the infection, certain types of cells, called memory cells, persist for years to protect against future attacks. If that happens, these few lingering cells will rally the troops and quickly make many copies to block the pathogen. Vaccines aim for this same result without the getting sick part.
The nuts and bolts of COVID-19 vaccine candidates
Groups around the world are evaluating more than 100 potential vaccines. These include many different technologies, some of which have been used for decades in polio, chickenpox, and other vaccines you might have received. Newer technologies have yet to prove themselves in licensed vaccines. What’s common for both categories is that most target the spike protein sprinkling the surface of each virus particle. The spike protein is an attractive target, as it’s instrumental in the ability of the virus particles to replicate. One portion of the spike protein attaches to cells in the infected human, called host cells. The other portion fuses with the cell membrane, serving as a door through which the virus enters the cell. Once inside, the virus will hijack the host cell’s machinery to make many copies that get released from the cell. Those can then infect other cells, and so on. The vaccines under development are being made against various parts of the spike protein.
Pathogen wanted: dead or alive
Established technology for vaccines uses the native ‘wild type’ pathogen — either live or inactivated. Live but weakened, or attenuated, vaccines are often quite effective. However, people with weakened immune systems, such as those taking chemotherapy, could get the full-blown infection. A traditional example of a live, attenuated vaccine is the measles vaccine, which got its start from virus isolated from 13-year-old David Edmonston in 1954. It took almost 10 years to transform the wild virus into a weakened version suitable for vaccination. At least two of the potential COVID-19 vaccines use live, attenuated virus.
Inactivated vaccines are usually made by inactivating the pathogen with heat or chemicals. These can include the whole pathogen or just a portion. Inactivated vaccines are designed to minimize the chance of getting sick. However, the response might not be as strong as for the live vaccine, and additional ‘booster’ shots are often needed. The vaccines for rabies and hepatitis A use inactivated virus. At least two COVID-19 vaccine candidates fall into this category.
These are the up-and-comers
The new technologies use genetic engineering and rely on the body’s own machinery to produce portions of the spike protein. For reference, here’s a drawing of the machinery for making proteins, including where the different steps take place within a cell:
Viral vectors are viruses that don’t cause disease and serve as vehicles to deliver DNA with instructions for making a pathogenic protein. The nonpathogenic virus replicates in the body, producing more copies of the virus including the pathogenic protein. This technology is relatively new, and only one vaccine, against Zaire ebolaviruses, is licensed for use in humans. That vaccine was a long time in the making — more than 15 years. Several COVID-19 candidates use viral vectors.
DNA-based technologies put the code for a pathogenic protein into a circular DNA called plasmids. One main challenge is the need to get the DNA across two membranes — cell and nuclear. Viral vectors and other options are being explored to deliver the DNA. No DNA-based vaccines are licensed for use in humans, but there are several being evaluated for COVID-19.
RNA- and protein-based technologies have the advantage that they do not need to cross the nuclear membrane of a host cell. However, RNA is particularly unstable so is not injected alone. Both RNA and protein are frequently delivered inside a fat, or lipid, cocoon called a nanoparticle. Although there are no licensed examples for humans, several COVID-19 candidates use these technologies. Among these are a ‘molecular clamp’ version featured on the Discovery Matters podcast.
The future
It will be interesting to see which COVID-19 vaccine candidates exit phase 3 clinical trials and are licensed. Do you think the new technologies will edge out their live and inactivated counterparts? Time will tell.
Speaking of time…To learn why it takes so long to make a vaccine, give my previous article a quick read. Also, check out this podcast episode on the artistry of vaccine development.
Resources
Gavi, the Vaccine Alliance. How do vaccines actually work? https://www.gavi.org/vaccineswork/how-do-vaccines-actually-work. Published August 10, 2020. Accessed September 2, 2020.
Mayo Clinic. COVID-19 (coronavirus) vaccine: Get the facts. https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/coronavirus-vaccine/art-20484859. Published June 10, 2020. Accessed September 2, 2020.
Children’s Hospital of Philadelphia. Questions and answers about COVID-19 vaccines. https://www.chop.edu/centers-programs/vaccine-education-center/making-vaccines/prevent-covid. Published August 24, 2020. Accessed September 2, 2020.
McKeever A. Dozens of COVID-19 vaccines are in development. Here are the ones to follow. National Geographic. https://www.nationalgeographic.com/science/health-and-human-body/human-diseases/coronavirus-vaccine-tracker-how-they-work-latest-developments-cvd/. Published September 3, 2020. Accessed September 8, 2020.
Craven J. COVID-19 vaccine tracker. Regulatory Affairs Professional Society. https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-vaccine-tracker. Published August 27, 2020. Accessed September 2, 2020.
