The Case for Individual Decision-Making in COVID Vaccination Strategies

The challenge

“The Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) today unanimously recommended that vaccination for COVID-19 be determined by individual decision-making.” 

– Department of Health and Human Services

Echoing the Great Barrington Declaration’s call for “focused protection,” the World Health Organization has, since March 2023, stopped recommending routine boosters for people at only moderate or low risk and instead urges priority coverage for those most vulnerable. To put that targeted strategy on a solid footing and inform individual decision-making, we need precise, individual-level data on how immunity waxes and wanes, insights that might let us pinpoint who loses protection fastest—and who should be first in line when the next round of shots rolls out.

The study, building on a focused protection approach, tracked 2500 people in rural Japan during the Alpha and Omicron COVID waves. Nearly all individuals received the standard two-dose course of Pfizer’s vaccine, with a smaller number receiving Moderna’s vaccine. Researchers mapped their immune response over a period of about 18 months. Antibody titers and their longitudinal trajectories were anything but uniform; some people held sky-high levels for months, others never rose far, and many sat in between. Boosters lifted everyone, even for the immunocompromised and elderly, but while the booster buys extra headroom, the countdown to decline continues.

The researchers, using the rise and fall of antibody titers, categorized six groups: three with archetypal patterns and three intermediate. 

• Durable “good responders” with antibody levels remaining high for months, offering the strongest protection. Most are in their late 30s to late 50s, proving sustained immunity isn’t restricted to the very young. The booster lifts their antibody levels and keeps them high.
• Rapid declining “poor responders” whose antibody titers soar early but plunge quickly, leaving only moderate immune defense. The group is primarily composed of adults in their 30s and 40s, indicating that even younger cohorts can lose protection quickly. Antibody titers surge after the booster, but like the original immunization, slide quickly
• Vulnerable “poor responders” whose titers start and stay low, translating into the weakest neutralization against the earliest COVID strains. While the cohort’s average age was around 68, middle-aged participants also appeared, highlighting an added risk that isn’t confined to the elderly. Boosters raise the titers, but in keeping with their overall immunologic response, the rise is less, leaving them the weakest but better than before.

Roughly 60% of the “durable” remained durable after the booster, but the other 40% slipped into less robust categories. Meanwhile, more than half of the initial vulnerable group and over a third of the rapid decliners remained stuck in their same low-protection patterns despite receiving the extra shot. Overall, past performance was no guarantee of future results, as half of the patients changed categorization. The amount of antibody present at the time of the boost showed only a weak correlation with subsequent levels. 

The most vigorous defense was seen in women, and anyone who felt post-shot side effects; chronic conditions (diabetes, heart disease, hypertension) dampened the response. Mixing vaccine brands pushed titers higher. Cellular immunity tracks the same durability hierarchy as antibodies

Large studies agree that a bout of COVID-19 leaves behind meaningful—but far from uniform—protection. Meta-analyses indicate that natural immunity reduces the risk of symptomatic reinfection by approximately two-thirds overall. In the Fukushima cohort, prior infection did boost peak antibody levels; yet, those “recovered” volunteers still fell into the same durable, intermediate, and vulnerable response groups as infection-naïve participants, showing that infection alone doesn’t guarantee a high or long-lasting immune trajectory. Overall infection rates were low and virtually identical across groups (≈5–6 %), yet when people became infected, differed sharply: every infection in the rapid-decliner group occurred within 200 days, whereas the other groups saw infections spread out over the whole study interval. The trajectory of each person’s immune response, as measured by their antibodies, was a better predictor of breakthrough infections and their timing than any single moment in our immune defenses. Interestingly, the researchers found that IgA levels, which are concentrated in nasal defenses, were the most effective single measure of the booster response and could be obtained from a single serum sample. 

The Big Picture

COVID immunization rates are declining for various reasons, but protection for those at risk and the immunocompromised remains a public health priority. The study provides some data-driven groupings, with three standouts:

• Durable—antibodies and T-cells stay high (≈ 30 % of people).
• Rapid-decliner—big early spike, quick fade (≈ 15 %).
• Vulnerable—low from the start (≈ 15 %).

Everyone else sat in intermediate territory—a single serum IgA measurement soon after the booster, flagged who would later get a breakthrough infection. Data-driven immune profiling—and a simple IgA blood test—could refine medical decision-making regarding who receives future COVID-19 boosters and when. The work has limitations, most notably that it covers only one of the multiple booster rounds we experienced, and COVID-19 shape-shifts, so that the patterns with one variant may differ from those with others. 

The findings are clear: roughly one-third of people stay well-protected, one-third drift into middling territory, and the rest either plunge quickly or never rise far at all—and a simple post-booster IgA blood test can flag who is on the risky paths. Sharing such individual-level metrics, rather than broad averages, is the key to making “individual decision-making” more than a slogan and to ensuring boosters reach the people who genuinely need them most. It is not sufficient to simply recommend individual decision-making when we do not widely share the data or craft guidance that helps to frame those individual discussions. 

Source: Longitudinal antibody titers measured after COVID-19 mRNA vaccination can identify individuals at risk for subsequent infection Science Translational Medicine DOI: 1126/scitranslmed.adv4214