On the day two healthcare workers received their COVID‑19 shots, both displayed robust early antibody levels. Six months later, one remained disease‑free while the other contracted the virus. A new Science Translational Medicine study offers clues to this difference.
Scientists recorded post‑vaccination IgG antibody titres in 2,526 participants over 18 months to watch how the immune response evolved from the first dose through subsequent boosters. Using long‑term data and machine‑learning analysis, they classified the responses into four distinct trajectories, becoming the first to map a “rapid‑decliner” cohort systematically.
The identified patterns are: Durable responders – maintained high antibody levels; Rapid‑decliners – began with strong titres that fell quickly; Vulnerable responders – produced low antibody amounts that also declined fast; and Intermediate responders – fell somewhere in between.
Senior author Shingo Iwami of Nagoya University’s Graduate School of Science expressed surprise at the rapid‑decliner group. He noted, “Although they started with a potent response, these individuals experienced infection sooner than others. A single IgG test can’t anticipate this risk; continuous monitoring reveals the pattern.”
Breakthrough infections—cases occurring after vaccination when the virus overcomes vaccine‑induced immunity—were slightly more frequent among those with swift antibody drops, either from low initial levels or rapid decline.
After the booster schedule, 29% were durable responders, 28% vulnerable responders, 19% rapid‑decliners, and the remainder fell into the intermediate category. Breakthrough infection rates varied modestly: 5.2% for durable responders versus 6% for vulnerable and rapid‑decliners.
Researchers also discovered that participants who had breakthrough infections had lower blood levels of IgA(S) antibodies several weeks post‑vaccination. These antibodies play a key role in protecting the nasal and throat mucosa, our first line against respiratory viruses.
Importantly, the study showed a strong correlation between circulating IgA(S) and nasal IgA(S) levels, suggesting that a blood test can reliably indicate airway immunity. Thus, measuring IgA(S) soon after vaccination could flag individuals at higher risk, especially within vulnerable groups.
While the findings lay groundwork for future work, Iwami highlighted the need to uncover biological drivers of rapid antibody loss—factors such as age, genetics, vaccine characteristics, and lifestyle elements like sleep, stress, or concurrent medications. He emphasized that clear categorization of vaccine responses “helps explain why some people may require boosters sooner than others.”
“Understanding these patterns could enable more personalized vaccination strategies,” Iwami added, noting that widespread antibody testing would depend on cost, accuracy, and comparative benefit over existing approaches. Further research is required to fully assess the potential of this strategy.