Abstract
A primary series of Sinovac COVID-19 vaccine (CoronaVac) and ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccine successfully increased anti-spike antibodies, neutralizing antibodies, and T-lymphocytes, as was also observed following booster doses of Oxford-AstraZeneca or BNT162b2 (Pfizer-BioNTech) vaccine. However, information regarding the dynamics of specific B- and T-lymphocytes induced by additional vaccinations remains limited. We examined the dynamics of specific B- and T-lymphocyte subsets induced by primary series vaccinations and booster doses over a two-year period of COVID-19 vaccination among healthcare personnel (HCP) enrolled in a prospective cohort study in Thailand. HCP, recruited between January and March 2021, had blood specimens collected at enrollment and at three-month intervals for cellular immune response testing. COVID-19 vaccinated participants (verified against documentation) were grouped by vaccination schedules: (A) CoronaVac with Oxford-AstraZeneca vaccine as the first booster dose (n = 46), (B) CoronaVac with Pfizer-BioNTech vaccine as the first booster dose (n = 53), and (C) Oxford-AstraZeneca vaccine (n = 29). All three groups had up to four subsequent booster doses of either the same or different platforms. Following the B-lymphocyte enzyme-linked immunospot and the T-lymphocyte intracellular cytokine staining assays, SARS-CoV-2 spike 1 (S1)- and receptor-binding domain (RBD)-specific antibody-secreting B-lymphocytes, and Interferon Gamma (IFN-Ƴ)- and/or Tumor Necrosis Factor Alpha (TNF-α)-producing T-lymphocytes for all blood collection time points were counted. Among participants without evidence of infection (i.e., those who tested negative for SARS-CoV-2 antibodies prior to vaccination and those who tested negative by SARS-CoV-2 real-time reverse transcription polymerase chain reaction during the study), levels of cellular immune response during weeks 1-12 since the last vaccine dose were compared between vaccine doses using the Kruskal-Wallis test. In all three groups, compared to the primary series, the first booster dose induced significant SARS-CoV-2 antigen-specific antibody-secreting B-lymphocyte counts (range 4.2-9.0-fold increase) but non-significant S1-specific cytokine-producing T-lymphocyte counts (range 0.5-1.3-fold). There were no notable differences in both antigen-specific antibody-secreting B-lymphocyte and specific cytokine-producing T-lymphocyte counts following the second, third, and fourth booster doses in all three groups compared to the first booster dose. Initial COVID-19 booster doses were essential for overall increases in the peak counts of antigen-specific B-lymphocytes, prior to minimal contraction phases occurred following additional boosters, while antigen-specific T-lymphocyte counts maintained a consistently high levels of immune response. The second, third, and fourth booster doses restored the levels of both B- and T-lymphocytes after the immune responses waned in a time-dependent manner.