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

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.
Chronic respiratory disease
Care/Management
Advocacy

Authors

Mazarakis Mazarakis, Toh Toh, Batmunkh Batmunkh, Anderson Anderson, Quah Quah, Ng Ng, Amraa Amraa, Burentogtokh Burentogtokh, Jigjidsuren Jigjidsuren, Altangerel Altangerel, Namjil Namjil, Mashbaatar Mashbaatar, Carissa Carissa, Luu Luu, Moore Moore, Neal Neal, Nguyen Nguyen, Li Li, Hart Hart, Do Do, Justice Justice, Mulholland Mulholland, von Mollendorf von Mollendorf, Licciardi Licciardi
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