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Front Immunol . Cellular immune responses 12 months after fractional or standard dose BNT162b2 booster vaccination in Mongolian adults

tetano

Editor, Senior Moderator
Front Immunol


. 2026 Apr 22:17:1779435.
doi: 10.3389/fimmu.2026.1779435. eCollection 2026.
Cellular immune responses 12 months after fractional or standard dose BNT162b2 booster vaccination in Mongolian adults

Nadia Mazarakis[SUP] 1 2 [/SUP], Zheng Quan Toh[SUP] 1 2 [/SUP], Tsetsegsaikhan Batmunkh[SUP] 3 [/SUP], Jeremy Anderson[SUP] 1 2 [/SUP], Leanne Quah[SUP] 1 [/SUP], Yan Yung Ng[SUP] 1 [/SUP], Otgonjargal Amraa[SUP] 3 [/SUP], Tsogjargal Burentogtokh[SUP] 4 [/SUP], Sarantsetseg Jigjidsuren[SUP] 4 [/SUP], Bolor Altangerel[SUP] 5 [/SUP], Narantuya Namjil[SUP] 5 [/SUP], Khaliunaa Mashbaatar[SUP] 3 [/SUP], Rachael Carissa[SUP] 1 [/SUP], Skyy Luu[SUP] 1 [/SUP], Kerryn A Moore[SUP] 1 [/SUP], Eleanor F G Neal[SUP] 1 2 [/SUP], Cattram Nguyen[SUP] 1 [/SUP], Shuo Li[SUP] 1 [/SUP], John Hart[SUP] 1 [/SUP], Lien Anh Ha Do[SUP] 1 2 [/SUP], Frances Justice[SUP] 1 [/SUP], Kim Mulholland[SUP] 1 2 6 [/SUP], Claire von Mollendorf[SUP] 1 2 [/SUP], Paul V Licciardi[SUP] 1 2 [/SUP]


Affiliations
Abstract

Despite the role of booster doses in sustaining protection against emerging SARS-CoV-2 variants, global uptake remains low, highlighting the need for dose-sparing strategies that maintain durable immunity. We conducted a randomized controlled trial in Mongolian adults to examine long-term cellular immune responses to standard and fractional doses of BNT162b2 given as a third dose. A total of 601 participants, primed with ChAdOx1-S, BBIBP-CorV, or Gam-COVID-Vac, were randomized (1:1) to receive 15 μg (fractional dose) or 30 μg (standard dose) of BNT162b2. A subset of participants (N = 256) were enrolled for cell-mediated immunity analysis (n = 101 ChAdOx1-S primed, n = 117 BBIBP-CorV primed, n = 38 Gam-COVID-Vac primed). Antibodies were measured for binding anti-Spike IgG and neutralizing antibodies, and T-cell responses were measured using activation-induced marker (AIM), intracellular cytokine staining (ICS), and IFN-γ against SARS-CoV-2 Spike-specific wild-type and JN.1, and followed-up for 12 months. At 12 months post-vaccination, wild-type and JN.1 IgG levels were sustained and remained approximately 1.7-2.7-fold higher than baseline levels, and neutralizing antibodies were maintained (89% inhibition) for each priming stratum and standard and fractional dose groups. Across all study visits, total AIM CD4mem (expressing CD69+, OX40+, or CD137+) and CD8mem (CD69+CD137+), total ICS CD4mem and CD8mem (IL-2+, TNF-α+, or IFN-γ+), and ELISpot IFN-γ remained similar by study arm and priming strata for wild-type and JN.1 responses. CD4mem AIM responses peaked 6 months post-vaccination; by 12 months, responses to wild-type were maintained, whereas JN.1 responses had declined to day 28 levels or lower. For memory T-cell ICS responses, durability was maintained over 12 months post-vaccination for both wild-type and JN.1 responses. Overall, fractional booster dosing produced comparable and robust long-term humoral and cellular immune responses to a standard dose, including against the JN.1 variant.

Keywords: COVID-19; cellular immune response; immunology; longitudinal; vaccine.

 
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