Primary immune trajectories following a single BNT162b2 vaccination scheme in SARS-CoV-2–naïve individuals

mRNA vaccines have shown high efficacy against SARS-CoV-2, yet orchestration of innate and adaptive responses in infection-naïve individuals remains incompletely characterized. Understanding these dynamics in people without prior infection is essential for defining baseline immune trajectories and providing a reference for future studies. We conducted a longitudinal study in SARS-CoV-2-naïve adults who received two doses of the BNT162b2 vaccine. Peripheral blood was analyzed by flow cytometry to quantify monocyte, NK, T, and B cell subpopulations, and serum cytokines were measured by multiplex assays. Data were evaluated with Z-score normalization and paired comparisons. Monocyte subsets segregated into two groups: one with progressive decline and another with transient activation. NK cells displayed multiphasic activation, particularly after booster. CD4+ and CD8+ T cells differentiated toward central and effector memory phenotypes, while B cells showed evidence of germinal center engagement followed by memory refinement. Cytokine fluctuations, including interferon-related signals, paralleled cellular dynamics. The booster was associated with re-engagement of innate components and amplification of adaptive responses. BNT162b2 vaccination in naïve individuals induces a coordinated sequence in innate and adaptive compartments, culminating in memory T and B cells. These findings align with current literature and provide trajectories to inform immune monitoring and optimization strategies.