A work just published in the journal Nature shows that the second dose of the Pfizer COVID-19 vaccine induces a very powerful response in a part of the immune system that provides extensive antiviral protection.
“This is the first time that RNA vaccines have been administered to humans, and we have no idea how they do what they do: offer 95% protection against COVID-19,” explains Bali Pulendran, a researcher at Stanford University and co-author of the work. “So we decided to analyze in great detail the immune response induced by one of these vaccines, the one marketed by Pfizer Inc.”
Traditionally, the main immunological basis for the approval of new vaccines has been their ability to induce neutralizing antibodies – individualized proteins, created by immune cells called B cells, that can attach to a virus and block it from infecting cells. “Antibodies are easy to measure,” explains Pulendran. But the immune system is much more complicated than that. Antibodies alone do not fully reflect their complexity and degree of protection. “
In December 2020, Stanford University School of Medicine began administering the Pfizer vaccine, and the team of scientists took this opportunity to conduct their study. They selected 56 healthy volunteers and took blood samples from them at various times before and after the first and second injections.
They counted antibodies, measured levels of immune signaling proteins, and characterized the expression of each gene in the genome of 242,479 independent immune cell types and states. A key component of the immune system the team examined were T cells – immune cells that don’t stick to viral particles like antibodies do, but instead scan body tissues for cells that show telltale signs of viral infections . When they find them, they destroy those cells.
Furthermore, we now know the importance of the innate immune system, a variety of first responders cells. “ It is the sixth sense of the body ”, explains Pulendran, “its constituent cells are the first to notice the presence of a pathogen. Although they are not good at distinguishing between separate pathogens, they secrete signaling proteins that launch the response of the adaptive immune system – the B and T cells that attack specific viral or bacterial species or strains. During the week or so it takes for the adaptive immune system to ramp up, innate immune cells perform the critical task of keeping incipient infections at bay by indiscriminately attacking any foreign element that resembles a pathogen. “
A new type of vaccine
RNA vaccines work quite differently than classic vaccines made up of live or dead pathogens, individual proteins, or carbohydrates that train the immune system to target a particular microbe and kill it. Instead, the Pfizer and Moderna vaccines contain genetic recipes to make the spike protein that SARS-CoV-2, the virus that causes COVID-19, uses to attach itself to the cells it infects.
The researchers found that the first injection increases the levels of specific antibodies to SARS-CoV-2, as expected, but not as much as the second dose, which also has other effects that are hardly observed in the first. “The second dose stimulated a large increase in antibody levels, an excellent T cell response that was absent after the first injection, and a surprisingly enhanced innate immune response,” explains the researcher. The RNA vaccine, in particular the second dose, elicited the massive mobilization of a newly discovered group of normally sparse and inactive first responder cells.
First identified in a recent study led by Pulendran, they are a small subset of monocytes that express high levels of antiviral genes and that barely move in response to an actual COVID-19 infection. But the Pfizer vaccine, however, induced its activation. This special group of monocytes, which are part of the innate immune system, made up only 0.01% of all circulating blood cells before vaccination. But after the second injection of the Pfizer vaccine, their number multiplied by 100 to represent 1% of all blood cells. Furthermore, his disposition became less inflammatory but more intensely antiviral. “They seem exceptionally capable of providing extensive protection against various viral infections,” explains the expert. “The extraordinary increase in the frequency of these cells, just one day after the booster immunization, is surprising. It is possible that these cells could mount a retention action not only against SARS-CoV-2 but also against other viruses . “