A study from Stanford Medicine is shedding new light on how the COVID-19 vaccine works. The research emphasizes the importance of the second dose, finding that it provides far more antiviral protection than the first dose.
“Despite their outstanding efficacy, little is known about how exactly RNA vaccines work,” said study co-senior author Dr. Bali Pulendran. “So we probed the immune response induced by one of them in exquisite detail.”
The experts set out to investigate how the Pfizer vaccine affects numerous components of the immune response. The study was focused on antibodies and immune cells in blood samples from individuals who had been inoculated with the vaccine.
“The world’s attention has recently been fixed on COVID-19 vaccines, particularly on the new RNA vaccines,” said Dr. Pulendran. “This is the first time RNA vaccines have ever been given to humans, and we have no clue as to how they do what they do: offer 95% protection against COVID-19.”
The traditional approach to approving new vaccines looks at their ability to induce neutralizing antibodies, which are individualized proteins created by immune cells that can block a virus from infecting cells.
“Antibodies are easy to measure,” said Dr. Pulendran. “But the immune system is much more complicated than that. Antibodies alone don’t come close to fully reflecting its complexity and potential range of protection.”
The researchers analyzed how every type of immune cell was influenced by the vaccine, including their numbers, their activation levels, the genes they express, and the proteins and metabolites they produce.
The team looked closely at the response of T cells, “search-and-destroy” immune cells that probe the body for cells associated with viral infection.
The researchers found that the first dose of the Pfizer vaccine increases SARS-CoV-2-specific antibody levels, but not nearly as much as the second dose, which turned out to be far more powerful in other ways as well.
“The second shot has powerful beneficial effects that far exceed those of the first shot,” said Dr. Pulendran. “It stimulated a manifold increase in antibody levels, a terrific T-cell response that was absent after the first shot alone, and a strikingly enhanced innate immune response.”
According to Dr. Pulendran, the second dose of the vaccine was particularly responsible for the massive mobilization of a newly discovered group of first-responder cells that are normally scarce.
The cells were first identified in a recent vaccine study led by Dr. Pulendran. While they barely responded to an actual COVID-19 infection, they became 100 times more prevalent after the Pfizer vaccine. Dr. Pulendran said the cells seem uniquely capable of providing broad protection against diverse viral infections.
“The extraordinary increase in the frequency of these cells, just a day following booster immunization, is surprising,” said Dr. Pulendran. “It’s possible that these cells may be able to mount a holding action against not only SARS-CoV-2 but against other viruses as well.”
The study is published in the journal Nature.