A brief review of the COVID vaccines

RBC | This article is directed toward readers who may have lingering concerns about vaccine safety, those who are confused by misinformation circulating on the web, and anyone interested in the basic biology of vaccination. This is, particularly, the remarkable story of the new mRNA vaccines. I can’t cover all the details. Three short animations help to illustrate the processes I describe; readers can find links to them at the end of the article.

Screenshot from a Harvard University public health animation explaining how mRNA vaccines work

In the following brief sketch of the viral life cycle and the body’s immune response, ‘virus’ refers specifically to SARS-CoV-2, the coronavirus that causes the disease COVID-19, and ‘cell’ refers to the human cells it attacks. While the discussion is specific to SARS-CoV-2, other viral infections follow the same general pattern.

Viruses take over normal cells’ replication machinery and use it to produce more viruses, which then infect other cells. Disease results from the damage to those previously healthy cells and also as a side effect of the body’s own inflammatory response.

There are several steps in the life cycle of a virus. First it has to stick to the surface of a cell, e.g. a cell in the lining of the airway. That’s where the coronavirus spike protein comes in. It binds to a protein common to the surface of human cells. If you can prevent that binding, you prevent infection and disease.

After binding, the virus has to gain entry into the cell. Binding of the coronavirus spike protein initiates a series of events by which the cell pulls the virus inside.

Then the virus takes over the cell’s own replication and transcription machinery to produce new viral RNA and new viral proteins. (RNA is the genetic blueprint for making new copies of the virus.) Those proteins self-assemble into new virus particles, encapsulating the new viral RNA. The new viruses burst out of the cell, destroying it, and disperse to infect other cells.

The body’s immune system responds to a new infection and then creates a memory bank to react to future infections more quickly.

As with any pathogen, our immune systems jump into action if there’s a COVID infection. Specialized T-cells recognize the viral spike protein displayed on the surface of infected cells and on other antigen-presenting cells of the immune system, the cellular scouts out on the body’s defensive perimeter. Those T-cells release signaling and activating chemicals that recruit killer cells, which destroy anything carrying the spike protein. Other chemical signals from the T-cells activate B-cells which produce antibodies to the spike protein. (Antibodies are specialized defensive proteins produced by the immune system.) Those antibodies stick to the spike protein. That prevents the spike protein from binding to new cells and infecting them. Antibodies bound to the spike protein also activate other chemical cascades and attract other immune cells that destroy any virus or cell carrying the viral spike protein. Meanwhile, inflammation brings more immune cells and antibodies into an infected region. After the infection is cleared, memory T-cells remain in the circulation and in lymph nodes, ready to activate a response to any repeat infection by that strain of virus.

Vaccines activate the immune system and create protective immune memory using weakened or killed virus or, with the newly available technologies, by activating production of the spike protein without the presence of the actual virus.

The Johnson&Johnson and AstraZeneca vaccines carry the spike protein into the body using adenovirus vectors, viruses that themselves do not cause disease. The mRNA vaccines (Moderna and Pfizer), on the other hand, employ a system that delivers a snippet of coronavirus RNA into the cells. That snippet carries the RNA blueprint for the spike protein. Just as they do with their own RNA to produce normal cellular proteins, those injected cells produce the viral spike protein, and the immune system responds as it would to the spike protein in a real infection. That ramps up immune defenses, as outlined above, and over time creates memory cells that can recognize and obliterate the real virus. In some people, the inflammatory response also gets activated; that’s what causes the common side effects of soreness at the injection site or flu-like symptoms for a day or two.

Same as in their normal day-to-day protein production, the spike-producing cells inactivate viral mRNA in a few minutes to hours. There’s no lingering viral mutant monster.

It’s important to note that the new mRNA vaccine technology is exactly replicating the same cellular mechanics and the same immune response as would result from the real coronavirus infection, except there’s not a complete RNA genome to build whole virus. There’s only the RNA segment for the spike protein. That’s what the immune system responds to. That’s what prevents infection with the real thing. And even more promising, the new technologies enable rapid development of new vaccines to counter new variants of the spike protein or other antigens (viral proteins that activate the immune system).

The science that has produced these extraordinary vaccines is the result of nearly 70 years of research. We stand on the shoulders of giants dating back even further, to the early geneticists like Gregor Mendel and beyond. We are enormously fortunate to live in a time where a vaccine can be developed in just a few months, a vaccine that can stop a global pandemic.

One hundred years ago four out of 10 children born in the United States did not survive to adulthood. They died from smallpox and measles and diphtheria and pertussis and a host of other infectious diseases. (Other public health deficits certainly contributed to high infant and childhood mortality, but infectious diseases were top of the list.) Today, and unless we assume that it can never happen to us because it’s not happening now, children are protected by vaccination. They survive. Vaccines save lives. The COVID vaccines have undoubtedly prevented hundreds of thousands of deaths already. If enough of us get vaccinated, we can stop the pandemic.