Safety, immunogenicity, and breakthrough infection of nine homologous or heterologous COVID-19 vaccination booster regimens in healthy adults: A prospective study in Taiwan.

Publication date: Jun 18, 2025

The COVID-19 pandemic necessitated diverse vaccination strategies to enhance immune protection. This study aimed to evaluate the immunogenicity, reactogenicity, and breakthrough infection of nine distinct vaccination regimens involving homologous or heterologous second booster doses in a SARS-CoV-2-nacEFve population in Taiwan. From December 2021 to May 2022, 784 healthy adults who had completed either homologous or heterologous prime and first booster vaccinations received a second booster dose, resulting in nine vaccination combinations. Reactogenicity was monitored for seven days post-vaccination. Immunogenicity was assessed using Roche and Abbott anti-spike antibody assays and a surrogate virus neutralization test (sVNT) at baseline, one month, and six months post-booster. Breakthrough infections during a six-month follow-up period were recorded to evaluate vaccine performance. All regimens significantly boosted humoral immune responses at one month post-second booster. The homologous mRNA-1273 (MMM) group exhibited the highest antibody levels, despite participants having older age and more comorbidities. Antibody levels declined at six months across all groups, but the MMM group consistently maintained the highest levels. The protein subunit vaccine MVC-COV1901 induced lower antibody levels but demonstrated a favorable reactogenicity profile, with fewer systemic adverse events. Breakthrough infection rates varied among groups, with comparable infection risks observed in participants receiving mRNA-1273 or MVC-COV1901 boosters following a homologous ChAdOx1 primary vaccination. No severe infections, hospitalizations, or deaths were reported. Homologous and heterologous COVID-19 booster regimens are safe and effective, with mRNA-1273 providing the strongest humoral immunity. These findings support tailored booster strategies to maintain population immunity and manage the pandemic.

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