Even After Being Vaccinated, Did You Contract Covid-19 Again? New Study Shows Why

Japanese researchers followed more than 2,500 people for 18 months and discovered that part of the population loses immunity from the COVID-19 vaccine more quickly, even starting with high antibody levels. This "rapid decline group" has lower production of IgA antibodies, essential for protecting the nose and throat, and a higher risk of early infection. Monitoring these responses could allow for more personalized and effective booster strategies.

Defining who should receive booster doses of the COVID-19 vaccine remains a central issue in the post-pandemic phase. To date, revaccination decisions are mainly based on factors such as age and the presence of chronic diseases.

However, these strategies do not take into account the individual immune profile, that is, how each person's immune system reacts and maintains its protection over time.

A large Japanese study, conducted by researchers at Nagoya University and carried out in Fukushima Prefecture, followed 2,526 people for 18 months, between April 2021 and November 2022, to answer this question.

Using mathematical modeling and artificial intelligence (AI), the scientists monitored antibody and T-cell responses after two initial doses and a booster dose of messenger RNA vaccines against SARS-CoV-2.

The team identified distinct patterns of immune response, grouping participants into four categories:

1. Long-lasting responders: exhibited high and stable antibody levels over time;

   
   

2. Vulnerable responders: had low antibody levels, which dropped rapidly;

   
   

3. Rapid-declining responders: started with high antibody levels but lost this protection rapidly;

   
   

4. Intermediate responders: fell between the other groups.

About half of the participants remained in the same group after the booster dose, showing that how the immune system reacts to the vaccine tends to be a personal and stable characteristic.

The rapid-declining group particularly caught the researchers' attention. Despite developing a very strong initial immune response, these individuals lost protection earlier and had a higher risk of early SARS-CoV-2 infection.

Four antibody response patterns were identified, with subsequent infections associated with lower levels of IgA(S) antibodies. Credit: Kana Ariga

Scientists observed that, in this group, levels of specific IgA antibodies against the spike protein, responsible for protecting the nose and throat, the main entry points for the virus, were significantly lower in the weeks following vaccination.

This finding is crucial because IgA antibodies (also called IgA(S), because they bind to the spike protein) are an essential part of the body's first line of immune defense against respiratory viruses. Low levels of these antibodies in the blood correlated strongly with low levels in the nasal passages, indicating that a simple blood test can serve as a reliable marker of actual protection against infection.

The results also revealed that, after booster doses, 29% of participants were classified as long-lasting responders, 28% as vulnerable, 19% as rapidly declining, and the remainder showed intermediate responses.

Post-vaccination infection rates varied little between groups (around 5% to 6%), but cases among individuals with a rapid decline in antibodies occurred earlier, suggesting greater vulnerability soon after peak immunity.

According to Professor Shingo Iwami, senior author of the study, “it was surprising to observe that people with very strong initial responses could lose that protection in a matter of months. This wouldn't be detected by a single antibody test; we could only perceive this pattern by tracking the evolution over time.”

In addition to revealing the phenomenon of “rapid decline,” the study proposes that continuous monitoring of antibody levels, especially IgA(S), can help health authorities identify who truly needs additional boosters and when.

This approach would allow for more personalized and efficient vaccination, avoiding both unnecessary revaccination and loss of protection in at-risk groups.

Although research has not yet determined why some people lose immunity more quickly, scientists suggest that factors such as age, genetics, type of vaccine, sleep quality, stress levels, and medication use may influence this decline.

The study provides a valuable basis for the future of immunization campaigns: understanding how individual immunity evolves is essential to maximizing population protection and optimizing public health resources. In a scenario of new variants and variable immunity, tracking antibody dynamics may be as important as measuring their quantity.

READ MORE:

Longitudinal antibody titers measured after COVID-19 mRNA vaccination can identify individuals at risk for subsequent infection

Hyeongki Park, Naotoshi Nakamura, Sho Miyamoto, Yoshitaka Sato, Kwang Su Kim, Kosaku Kitagawa, Yurie Kobashi, Yuta Tani, Yuzo Shimazu, Tianchen Zhao, Yoshitaka Nishikawa, Fumiya Omata, Moe Kawashima, Toshiki Abe, Yoshika Saito, Saori Nonaka, Morihito Takita, Chika Yamamoto, Hiroshi Morioka, Katsuhiro Kato, Ken Sagou, Tetsuya Yagi, Takeshi Kawamura, Akira Sugiyama, Aya Nakayama, Yudai Kaneko, Risa Yokokawa Shibata, Kazuyuki Aihara, Tatsuhiko Kodama, Akifumi Kamiyama, Tomokazu Tamura, Takasuke Fukuhara, Kenji Shibuya, Tadaki Suzuki, Shingo Iwami, and Masaharu Tsubokura

Science Translational Medicine, 17 Sep 2025, Vol 17, Issue 816

DOI: 10.1126/scitranslmed.adv4214

Abstract:

A key issue in the post–COVID-19 pandemic era is the ongoing administration of COVID-19 vaccines. Repeated vaccination is essential for preparing against currently circulating and newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. However, optimizing vaccination strategies is crucial to efficiently manage medical resources and establish an effective vaccination framework. Therefore, a strategy to identify poor responders with lower sustained antibody titers would be beneficial because these individuals should be considered high priority for revaccination. We investigated longitudinal antibody titer data in a cohort of 2526 people in Fukushima, Japan, collected between April 2021 and November 2022. Using mathematical modeling and machine learning, we stratified the time-course patterns of antibody titers after two primary doses and one booster dose of COVID-19 messenger RNA vaccines. We identified three populations, which we refer to as the durable, the vulnerable, and the rapid-decliner populations, and approximately half of the participants remained in the same population after the booster dose. The rapid-decliner population experienced earlier infections than the others. Furthermore, when comparing spike protein–specific immunoglobulin G (IgG) titers, spike protein–specific IgA titers, and SARS-CoV-2–specific T cell responses between participants who experienced subsequent infections after booster vaccination and those who did not, we found that spike protein–specific IgA titers were lower during the early stage after booster vaccination in participants who went on to become infected with SARS-CoV-2. This approach could be used to inform policy decisions on vaccine distribution to maximize population-level immunity both in future pandemics and in the post–COVID-19 pandemic era.