Fu, Jolene Yin LingSyed Omar, Sharifah FaridahRajasuriar, ReenaKukreja, AnjannaBasri, SazaliKamarulzaman, AdeebaTan, Cheng SiangSaid, AsriSu'ut, LelaLim, Soo KunJalalonmuhali, MaisarahBador, Maria KaharSam, I. ChingChan, Yoke FunWang, Lin FaCruz, Kristine Alvarado DelaYee, SidneyLu, Ho YuanRuifen, WengPandey, RahulYoung, BarnabySundar, RaghavSoebandrio, AminSawitri, Anak Agung SagungSutarsa, NyomanJantarabenjakul, WatsamonChan, NapapornTan, Chee WahVan Tan, LeChan, Yoke Fun2026-01-122026-01-120264-410XPubMed:40876143ORCID:/0000-0001-8261-2921/work/201884247https://hdl.handle.net/1885/733804179During the COVID-19 pandemic, Malaysia adopted heterologous vaccine booster strategies using BNT162b2 (Pfizer), CoronaVac (Sinovac) and ChAdOx1 nCoV-19 (AstraZeneca) due to vaccine shortages. However, longitudinal data on immune durability and breakthrough infections, especially in immunocompromised groups, remain limited. This study evaluates humoral response in healthy individuals after primary vaccine series and booster dose, and assesses long-term hybrid immunity up to two years post-booster in both healthy individuals and immunocompromised kidney transplant recipients (KTRs). BNT162b2 vaccine elicited a stronger anti-spike (anti-S) antibody response (3.0 log U/mL) compared to CoronaVac (1.6 log U/mL) at 3 months post-second dose. Anti-nucleocapsid (anti-N) antibody seroconversion was 50.3 % in CoronaVac recipients, suggesting limited humoral responses against N protein. Booster vaccination with homologous or heterologous mRNA-based regimens (BNT162b2/BNT162b2, ChAdOx1 nCoV-19/BNT162b2, and CoronaVac/BNT162b2) further enhanced anti-S antibody responses (3.6–3.7 log U/mL) for up to 6 months, whereas homologous CoronaVac/CoronaVac boosters yielded lower antibody levels (2.8 log U/mL). Breakthrough infections triggered a rapid rise in anti-N antibody, followed by a decline back to pre-infection levels within 3 months. In individuals infected two years after booster vaccination, T cell responses increased in healthy participants but declined in KTRs despite strong antibody responses, suggesting immunosuppressive therapy may impair T cell activation. These findings highlight the need for comprehensive immune assessments to guide preventive strategies, especially for immunocompromised populations.This work was supported by the ASEAN Science, Technology, and Innovation FUND (ASTIF) and Temasek Foundation [grant numbers IF061-2021], and Universiti Malaya matching grant [MG004-2022]. We thank all volunteers for participation in this study. We thank Muhammad Harith Pukhari for patient recruitment and sample collection. We would like to acknowledge Lu Mei Lee and Harvinder Kaur from Universiti Malaya Medical Centre for helping us with the sample processing using the Elecsys Anti-SARS-CoV-2 assay. All authors attest they meet the ICMJE criteria for authorship. This work was supported by the ASEAN Science, Technology, and Innovation FUND (ASTIF) and Temasek Foundation [grant numbers IF061-2021 ], and Universiti Malaya matching grant [ MG004-2022 ]. We thank all volunteers for participation in this study. We thank Muhammad Harith Pukhari for patient recruitment and sample collection. We would like to acknowledge Lu Mei Lee and Harvinder Kaur from Universiti Malaya Medical Centre for helping us with the sample processing using the Elecsys Anti-SARS-CoV-2 assay.enPublisher Copyright: © 2025 Elsevier LtdBoosterCOVID-19Humoral immunityKidney transplant recipientsPrimary vaccine seriesT cell immunity2025-09-1710.1016/j.vaccine.2025.127657105014537757