Medical, Microbiology Experts Discuss Science Behind Current COVID-19 Vaccines
"Study: COVID much more likely than vaccines to cause blood clots P - COVID-19—the actual disease—poses 8 to 10 times the threat of blood clots in the brain than do coronavirus vaccines, a large, non–peer-reviewed study led by University of Oxford researchers finds."
By Andrea Estrada for UCSB February 8, 2021 9:00 a.m.
Shortly after the COVID-19 pandemic broke out in early 2020, scientists and researchers around the world went to work to develop vaccines to fight SARS-CoV-2, the virus that causes COVID-19 disease.
On Dec. 11, the Food and Drug Administration (FDA) issued an emergency use authorization allowing Pfizer-BioNTech’s COVID-19 vaccine to be distributed in the U.S. A week later, a second vaccine, developed by Moderna, received the same FDA emergency use authorization.
The Current spoke with Dr. Scott Grafton, UC Santa Barbara’s COVID-19 coordinator and a distinguished professor in the Department of Psychological & Brain Sciences; and Chuck Samuel, the Charles A. Storke Professor and Distinguished Professor Emeritus in the Department of Molecular, Cellular and Developmental Biology, about how the vaccines work, how effective they are and how scientists were able to make them available so quickly.
TC: Can you give us a lesson on how vaccines work in general?
SG: Over the course of our lives, our immune systems are constantly learning to differentiate between what is foreign to our bodies and what belongs there. Continual exposures in the gut, the lungs, sinuses, blood, skin and other organs help the immune system identify and remember viruses, bacteria, fungi and other potentially lethal entities.
The immune system finds specific targets on these agents and uses them to organize a response for their elimination. For viruses, the target is often a bit of protein on their surface that the immune system can recognize.
But the learning process can take a few days or more, and each time a person becomes infected with an unfamiliar virus there is a race between the speed at which the virus is copying itself and causing symptoms and the quickness of the immune system to learn about and act against it.
A key strategy behind all vaccines is to train the immune system to recognize the offending agent without infecting the person in a way that might cause harm. This has classically been done by creating a weaker version of the virus, one that still shows off a bit of protein the immune system learns to recognize, but doesn’t grow particularly well in the person. In that way the immune system easily wins the race. These are the “live-attenuated” vaccines commonly in use.
CS: Yes, the live-attenuated vaccine strategy was the classical approach that produced some great vaccines — measles and OPV polio are good examples.
How is the COVID-19 vaccine different?
CS: The CoV-2 is not a simple virus. Coronaviruses are the largest RNA viruses that we know in terms of genetic information. Their information is contained in roughly 30,000 nucleotides. The polio virus for comparison is about 7,500 and the measles virus is about 15,000.
The COVID-19 vaccine is different from the live-attenuated vaccines for measles or polio because the COVID-19 vaccine is not the whole virus. Rather, it is a small piece of the virus’s genetic code, or genome. One of the genes of the CoV-2 virus specifies a protein called spike. Spike is on the surface of the CoV02 virus and it is the target of protective antibodies generated by our immune system.
SG: Each virus is a small bag of RNA, the molecule with code for making proteins. Once inside the body, the RNA code from the virus produces proteins that hijack the cells and enslave them to make more virus. Sticking out of this “bag” of the SARS-CoV-2 virus are bits of proteins that look like spikes.
These spikes help the virus gain access to the inside of the cells that line a person’s blood vessels. The lungs, mouth and sinuses are significant points of entry.
Rather than creating an attenuated virus, the Moderna and Pfizer vaccine makers pursued an old and simple strategy that has finally come to technical fruition. They made artificial tiny bags out of fatty molecules and loaded them with the RNA code for making some of the spike. However, the bags don’t include all the other virus RNA that is required to make copies of itself.
When the bags of RNA are injected into the arm, the cells in the muscle incorporate the RNA and make the spikes. The immune cells detect these spikes, recognize them as foreign and memorize their shape. The pain in the arm a person feels a day after the shot is a result of the emergence of spikes on the person’s cells and the immune system being drawn into the area and learning their shape.
How the Vaccine Works
The second shot provides additional exposure of the spike to the immune system to train it further. With the memory that is formed, future exposures to the SARS-CoV-2 virus from other people will lead to a recognition by the immune system and a quick response, thereby protecting the individual. New data suggests the Moderna vaccine leads to immune memory lasting for at least a year.
The RNA vaccine is a clever approach because no virus grows in the body. The RNA injected into the muscle in the arm is a natural molecule the body can clear out over time. And, it cannot become part of a person’s DNA. There is nothing in the vaccine that can alter a person’s genetic code, nor the DNA of their ovum or sperm.
TC: Is this “new” vaccine technology?
CS: The mRNA vaccine approach is new. But the idea of a subunit, a small part of the virus as the basis of the vaccine is not new. There are two very successful vaccines that work as subunit vaccines. One is for hepatitis B — HBV — and one is for human papilloma virus — HPV.
Each of these is a subunit vaccine, where a virus protein component is expressed alone and then that protein subunit is what’s used as the antigen to generate the immune response in the vaccine. It’s a component of the virus, not the whole virus. Subunit vaccines are very safe and can be very effective.
That’s the conceptual strategy behind the new SARS-CoV-2 mRNA vaccines available from Moderna and Pfizer that Scott described, though our bodies make the protein from the vaccine-delivered mRNA.
How were the Pfizer and Moderna vaccines able to be developed so quickly, and how do they differ from one another?
CS: It was a year ago last week that the CoV-2 virus was identified, and a year ago this week that the RNA genome sequence was made available. In less than a year we got two mRNA vaccines that are fabulous in terms of providing protection against COVID-19.
They could be developed quickly because lots of years of research by a number of laboratories laid the foundations for understanding coronaviruses, for understanding different mechanisms of gene expression and for developing the tools of molecular biology to study genes and their products.
When this disease came along, all this background knowledge was mobilized in a very rapid way. It wasn’t starting from scratch. There was a good foundation of knowledge.
SG: Over the past 30 years, immunologists have learned what kinds of protein bits might be better than others at training the immune system. The technology for making lots of RNA in whatever sequence is desired has become commonplace.
Once the RNA of the SARS-CoV-2 virus was sequenced in early 2020, expert choices were made as to what part of the spike would be most important for the immunes system to recognize, and this determines what RNA code to package as a vaccine.
The choice of what bits of the spike code to include differ with the Pfizer and Moderna vaccines, but the difference seems to be inconsequential; both lead to superb protection from SARS-CoV-2.