Beginning in April 2020, when New York City was an early epicenter of the pandemic, they enrolled roughly 500 health care workers and their family members in a study called PARIS (Protection Associated with Rapid Immunity to SARS-CoV-2). Over three years, participants returned repeatedly to give blood, building a record of more than 8,000 visits. This unusually long and detailed follow-up let the researchers see what happens to immunity well past the early dip that shorter studies revealed.

What they found is that antibody levels follow two phases. In the first phase, antibodies fall quickly over the initial months. This is expected and reflects the normal life cycle of the immune cells that mount the body's first wave of defense. In a second phase, beginning around seven to nine months after vaccination, the decline slows dramatically and levels hold steady at a personal "set point." In other words, immunity does not keep fading toward zero; it stabilizes and persists. This pattern matches what scientists understand about how the immune system stores long-term protection in long-lived cells that take up residence in the bone marrow.

The study also clarified how prior infection and booster doses shape this protection. People who had been infected before getting vaccinated—so-called hybrid immunity—mounted faster, higher antibody responses and stabilized at a higher long-term level. Booster doses acted as an "equalizer," lifting the antibody levels of vaccinated people who had never been infected up to those of the hybrid-immunity group, and each booster nudged the long-term set point higher. The researchers also observed that a breakthrough infection in a previously uninfected, vaccinated person boosted antibodies about as much as an extra vaccine dose would. Throughout the study, people with hybrid immunity remained better protected against breakthrough infection, both before and after the Omicron variant emerged.

"Our data show that mRNA vaccine–induced antibody responses are long lasting—an initial waning phase is followed by a stabilization phase, which is exactly what we would expect from basic immune cell biology," says Dr. Simon. "This challenges the widespread assumption that this kind of immunity simply fades away."

These findings matter for how the public and clinicians think about COVID-19 vaccination and the timing of boosters. They help separate two issues that are often confused: a true loss of antibodies over time versus a virus that changes enough to evade existing antibodies. By showing that the antibodies themselves are durable, the work reframes "waning immunity" as a more nuanced story—and provides a model that other researchers can use to study the long-term durability of immune responses to vaccines more broadly.

The PARIS study was carried out by a collaborative team at the Icahn School of Medicine at Mount Sinai, together with the dedicated participants who returned for many visits over three years. The research was supported by the National Institute of Allergy and Infectious Diseases, the Centers of Excellence for Influenza Research and Response (CEIRR), the Collaborative Influenza Vaccine Innovation Centers (CIVICs), philanthropic donations, and institutional funds provided to the Mount Sinai Center for Vaccine Research and Pandemic Preparedness (C-VaRPP).