The second dose of a COVID-19 vaccine induces a powerful boost to a part of the immune system that offers broad antiviral protection, according to a study by researchers at Stanford University School of Medicine.
The results published in the journal Nature strongly support the view that the second blow should not be ignored. “Despite their exceptional effectiveness, little is known about how exactly RNA vaccines work,” said Bali Pulendran, professor of pathology and microbiology and immunology. “So we probed the immune response induced by one of them in exquisite detail.” Pulendran is also a fellow of the Institute for Immunity Transplantation & Infection and Stanford Bio-X and a faculty member of Stanford ChEM-H.
The study was designed to find out exactly what effects the vaccine, marketed by Pfizer Inc., has on the many components of the immune response. The researchers analyzed blood samples from individuals inoculated with the vaccine. They counted antibodies, measured levels of immune signaling proteins, and characterized the expression of each gene in the genome of 242,479 distinct immune cell types and statuses.
“The world’s attention has recently shifted to COVID-19 vaccines, especially newer RNA vaccines,” Pulendran said, adding that Violetta L Horton P shares primary authorship of the study with Kari Nadeau, MD, PhD, professor of the Naddisy Foundation. Pediatric Nutrition, Allergy, Immunology and Asthma and Professor of Pediatrics, and Purvesh Khatri, PhD, Associate Professor of Biomedical Informatics and Biomedical Data Science.
The principal authors of the study are Prabhu Arunachalam, PhD, principal investigator at the Pulendran laboratory; medical student Madeleine Scott, PhD, a former graduate student of Khatri’s lab; and Thomas Hagan, PhD, a former postdoctoral researcher at the Stanford lab in Pulendran and now an assistant professor at the Yerkes National Primate Research Center in Atlanta.
“This is the first time that RNA vaccines have been given to humans, and we have no idea how they do what they do: provide 95% protection against COVID-19,” said Pulendran. 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, which can attach themselves to a virus and prevent it from infecting. cells.
“Antibodies are easy to measure,” Pulendran said. “But the immune system is much more complicated than that. Antibodies alone do not fully reflect its complexity and potential range of protection.” Pulendran and his colleagues assessed the events among all types of immune cells influenced by the vaccine: their numbers, levels of activation, the genes they express, and the proteins and metabolites they make and secrete during the process. inoculation.
A key part of the immune system examined by Pulendran and his colleagues were T cells: search for and destroy immune cells that do not attach to viral particles like antibodies do, but instead probe the body’s tissues for cells carrying telltale signs of viral infections. By finding them, they tear these cells apart. In addition, the innate immune system, an assortment of first responder cells, is now recognized to be of immense importance.
It’s the body’s sixth sense, said Pulendran, whose constituent cells are the first to become aware of the presence of a pathogen. Although they are not good at distinguishing distinct pathogens, they secrete “starter” signaling proteins that initiate the response of the adaptive immune system – B and T cells that attack specific viral or bacterial species or strains. .
For about a week, it takes the adaptive immune system to speed up, innate immune cells do the essential job of keeping emerging infections at bay by engulfing – or pulling harmful substances, albeit a little indiscriminately, at – anything like a pathogen for them.
The Pfizer vaccine, like the one manufactured by Moderna Inc., works very differently from conventional vaccines made up of living or dead pathogens, individual proteins, or carbohydrates that cause the immune system to focus on and kill a particular microbe. . Instead, 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.
In December 2020, Stanford Medicine began delivering the Pfizer vaccine to people. This stimulated Pulendran’s desire to put together a full report on the immune response to it. The team selected 56 healthy volunteers and took blood samples from them at several times before and after the first and second shots. The researchers found that the first stroke increases the levels of SARS-CoV-2 specific antibodies, as expected, but not as much as the second stroke. The second shot also does things that the first shot doesn’t, or barely does.
“The second hit has powerful beneficial effects that far exceed that of the first hit,” Pulendran said. “It stimulated a multiple increase in antibody levels, a formidable T cell response that was absent after the first stroke alone, and a remarkably improved innate immune response.” Unexpectedly, Pulendran said, the vaccine – especially the second dose – caused massive mobilization of a newly discovered group of first responder cells that are normally rare and quiescent.
First identified in a recent vaccine study led by Pulendran, these cells – a small subset of generally abundant cells called monocytes that express high levels of antiviral genes – barely move in response to actual COVID infection. -19. But the Pfizer vaccines induced them. This special group of monocytes, which is part of the innate museum, made up only 0.01% of all circulating blood cells before vaccination. But after the second injection of Pfizer vaccine, their number increased by 100 to represent 1% of all blood cells. In addition, their disposition became less inflammatory but more intensely antiviral. They appear to be particularly capable of providing broad protection against various viral infections, Pulendran said. “The extraordinary increase in the frequency of these cells, just one day after the booster vaccination, is surprising,” Pulendran said. “It is possible that these cells are able to mount a maintenance action not only against SARS-CoV-2 but also against other viruses,” he added.