# Long-Term Dynamics of SARS-CoV-2 Variant-Specific Neutralizing Antibodies Following mRNA Vaccination and Infection

## TL;DR

This study tracks antibody responses to SARS-CoV-2 over three years after vaccination and infection, showing that boosters and hybrid immunity provide durable protection.

## Contribution

The study provides longitudinal data on neutralizing antibody dynamics against multiple SARS-CoV-2 variants over three years, including insights into hybrid immunity and immune evasion.

## Key findings

- Antibody levels peaked after the third vaccine dose and remained stable two years later.
- Hybrid immunity resulted in higher neutralization titers compared to vaccination alone.
- XBB variant showed the lowest neutralization, indicating strong immune evasion.

## Abstract

Understanding the long-term dynamics of SARS-CoV-2 neutralizing antibodies is critical for evaluating vaccine-induced protection and informing booster strategies. In this longitudinal study, we analyzed 114 serum samples from 19 individuals across six time points over a three-year period following mRNA vaccination (Comirnaty) and natural SARS-CoV-2 infection. Using pseudotype-based neutralization assays against nine SARS-CoV-2 variants, including major Omicron subvariants (BA.1–BA.5, BQ.1.1, XBB), and anti-S1 IgG ELISA, we observed that antibody levels peaked after the third vaccine dose and remained relatively stable two years later. Neutralization titers rose markedly after the second and third doses, with the highest neutralization observed at two years post-booster. Strong correlations were found between anti-S1 IgG levels and mean neutralization titers for pre-Omicron variants (r = 0.79–0.93; p < 0.05), but only moderate for Omicron subvariants (r ≈ 0.50–0.64). Notably, hybrid immunity (vaccination plus infection) resulted in higher neutralization titers at the final time point compared to vaccine-only participants. The lowest neutralization was observed against XBB, underscoring the immune evasiveness of emerging variants. These findings support the importance of booster vaccination and highlight the added durability of hybrid immunity in long-term protection.