Italian Study Alarmingly Finds That COVID-19 Vaccination Weakens T-Cell Defenses
Nikhil Prasad Fact checked by:Thailand Medical News Team Sep 09, 2025 8 hours, 58 minutes ago
Medical News: A new study reveals hidden immune vulnerabilities
Scientists from the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milan, the Istituto Nazionale Genetica Molecolare Romeo ed Enrica Invernizzi Milan, the North Italy Transplant Program Milan, and the University of Milan have uncovered surprising findings about how COVID-19 vaccines influence long-term immunity. While vaccines are claimed to provide strong protection against severe illness, this
Medical News report highlights that vaccinated individuals who later suffer breakthrough infections were found to have had weaker T-cell responses compared to those who stay uninfected.
Italian Study Alarmingly Finds That COVID-19 Vaccination Weakens T-Cell Defenses
The focus on T-cells and natural killer cells
The research team studied 32 vaccinated healthcare workers in Milan. Sixteen experienced a breakthrough infection after their booster dose, mostly during the Omicron BA.1 wave, while the other half remained infection-free. Blood samples were analyzed at three key points: one month after the second vaccine dose, one month after the booster, and (for infected participants) one to three months after testing positive. The scientists measured not just antibodies but also T-cell responses and the activity of natural killer (NK) cells, which are crucial immune cells that help fight off viral infections.
A worrying discovery in vaccinated individuals
The study showed that vaccinated people who later became infected had significantly reduced spike-specific CD4 T-cell responses after the booster shot compared to those who never got infected. In simple terms, their immune systems were less able to respond to the spike protein of the virus even after receiving the booster. These individuals also displayed higher levels of a marker called LAG-3, which is linked to T-cell exhaustion—a state where immune cells become less effective at defending the body.
How breakthrough infections reshaped immunity
Interestingly, once breakthrough infections occurred, the natural infection seemed to “reset” and strengthen the immune system. The infected group showed improved CD4 and CD8 T-cell responses as well as an expansion of memory-like NK cells (CD57+ NKG2C+), which are known for their ability to remember past infections and provide stronger defenses in the future. This suggests that while vaccines alone may not always stimulate durable T-cell immunity in everyone, natural infection can reawaken these protective mechanisms.
What this means for future vaccine strategies
These findings shed light on why some people get infected even after being fully vaccinated and boosted. The problem does not appear to lie in antibody levels—both groups showed similar amounts of anti-spike antibodies—but rather in the quality of their T-cell response. This highlights the importance of looking beyond antibodies when assessing vaccine effectiveness. The study also suggests that immune checkpoint m
arkers like LAG-3 and the presence of memory-like NK cells could serve as indicators of how well a person’s immune system can actually respond to new infections.
Final thoughts
The results highlight that the ability of COVID-19 vaccines to generate strong and lasting T-cell responses may vary from person to person. For some individuals, this weakened T-cell immunity might make them more prone to breakthrough infections. However, natural infections—even if mild—appear to boost and restore immune strength, particularly through enhanced T-cell and NK cell activity. These insights stress the urgent need to design next-generation vaccines that better stimulate cellular immunity, not just antibody production. If researchers succeed, it could mean longer-lasting protection and fewer breakthrough cases in the future.
The study findings were published in the peer reviewed journal: Frontiers in Immunology.
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1657082/full
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