Abstract
We investigated how differences in age, sex, or vaccine type can affect humoral and cellular immune responses after vaccination with vector (ChAdOx1 nCoV-19), mix-and-match (first, ChAdOx1 nCoV-19, and second, BNT162b2), or mRNA (BNT162b2 or mRNA-1273) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Venous blood was collected from 573 subjects (vector, 396; mix-and-match, 96; and mRNA, 81) before the first vaccination ( T 0 ), 7 to 8 weeks (vector) or 3 to 4 weeks (mRNA) after the first vaccination ( T 1 ), and 3 to 4 weeks after the second vaccination ( T 2 ). The humoral and cellular immune responses were evaluated using Elecsys anti-SARS-CoV-2 (Roche), Alinity SARS-CoV-2 IgG II Quant (Abbott), cPass SARS-CoV-2 neutralization antibody detection (GenScript), and QuantiFERON SARS-CoV-2 (Qiagen) kits. At T 1 , the levels of the receptor-binding domain antibodies (RBD Ab) and neutralizing antibodies (NAb) decreased with aging, but interferon gamma release (IGR) levels increased. The RBD Ab, NAb, and IGR levels were higher in females than in males at T 1 and T 2 . The NAb levels were higher in the mix-and-match and mRNA vaccine groups than in the vector vaccine group at T 2 . The RBD Ab and IGR levels were higher in the mRNA vaccine group than in the vector or mix-and-match vaccine groups at T 2 . The optimal cutoffs for RBD Ab and NAb, which were used to determine the presence of T cell responses, were 5.7 binding antibody units per milliliter (BAU mL -1 ) and 12.0 IU mL -1 , respectively. Age, sex, and vaccine type affected the humoral and cellular immune responses, and T cell responses could be estimated from RBD Ab and NAb levels. IMPORTANCE There have been few studies that comprehensively evaluated factors affecting immune responses and the correlation between humoral and cellular immune responses after vector, mix-and-match, and mRNA vaccines against SARS-CoV-2. Therefore, we analyzed the effects of age, sex, and the different vaccine regimens on the immune responses to vaccination against SARS-CoV-2. The correlation between humoral and cellular immune responses and the cutoffs were derived for RBD antibodies and neutralizing antibodies to predict the presence of the cellular immune responses. In this comprehensive study, we demonstrated that there were differences in the immune responses induced after vaccination depending on the age and sex of an individual. Among the three vaccine regimens, the mix-and-match and mRNA vaccines induced the most robust immune responses. Finally, the proposed optimal cutoffs for RBD and neutralizing antibodies may be useful for predicting cellular immune responses when assays for cellular immune responses are not available.
Keywords: cellular immune responses; humoral immune responses; mRNA vaccine; mix-and-match vaccine; vector vaccine.
【저자키워드】 mRNA vaccine, humoral immune responses, cellular immune responses, vector vaccine., mix-and-match vaccine, 【초록키워드】 neutralizing antibody, SARS-CoV-2, Vaccine, coronavirus, immune response, vaccination, antibody, Cellular immune response, mRNA-1273, Sex, anti-SARS-CoV-2, immune, BNT162b2, Antibody detection, RBD, BAU, mRNA, immune responses, T cell responses, male, female, age, correlation, group, Roche, predict, SARS-CoV-2 IgG, T cell response, ChAdOx1 nCoV-19, SARS-CoV-2 neutralization, interferon gamma, cellular, humoral, Abbott, regimen, venous blood, acute respiratory syndrome, Factor, second vaccination, subject, regimens, Cutoff, Qiagen, first vaccination, QuantiFERON, Genscript, Effect, Affect, vaccine group, robust, analyzed, affected, investigated, evaluated, was collected, were used, determine, demonstrated, the receptor-binding domain, affecting, age and sex, binding antibody unit, Elecsy, 【제목키워드】 SARS-CoV-2, mRNA, vector, response, relationship,