Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany.
Institute of Medical Microbiology and Virology, University Medical Center Göttingen, Göttingen, Germany.
Allergy. 2022 Aug;77(8):2381-2392. doi: 10.1111/all.15247. Epub 2022 Feb 16.
Homologous and heterologous SARS-CoV-2 vaccinations yield different spike protein-directed humoral and cellular immune responses. This study aimed to explore their currently unknown interdependencies.
COV-ADAPT is a prospective, observational cohort study of 417 healthcare workers who received vaccination with homologous ChAdOx1 nCoV-19, homologous BNT162b2 or with heterologous ChAdOx1 nCoV-19/BNT162b2. We assessed humoral (anti-spike-RBD-IgG, neutralizing antibodies, and avidity) and cellular (spike-induced T-cell interferon-γ release) immune responses in blood samples up to 2 weeks before (T1) and 2-12 weeks following secondary immunization (T2).
Initial vaccination with ChAdOx1 nCoV-19 resulted in lower anti-spike-RBD-IgG compared with BNT162b2 (70 ± 114 vs. 226 ± 279 BAU/ml, p < .01) at T1. Booster vaccination with BNT162b2 proved superior to ChAdOx1 nCoV-19 at T2 (anti-spike-RBD-IgG: ChAdOx1 nCoV-19/BNT162b2 2387 ± 1627 and homologous BNT162b2 3202 ± 2184 vs. homologous ChAdOx1 nCoV-19 413 ± 461 BAU/ml, both p < .001; spike-induced T-cell interferon-γ release: ChAdOx1 nCoV-19/BNT162b2 5069 ± 6733 and homologous BNT162b2 4880 ± 7570 vs. homologous ChAdOx1 nCoV-19 1152 ± 2243 mIU/ml, both p < .001). No significant differences were detected between BNT162b2-boostered groups at T2. For ChAdOx1 nCoV-19, no booster effect on T-cell activation could be observed. We found associations between anti-spike-RBD-IgG levels (ChAdOx1 nCoV-19/BNT162b2 and homologous BNT162b2) and T-cell responses (homologous ChAdOx1 nCoV-19 and ChAdOx1 nCoV-19/BNT162b2) from T1 to T2. Additionally, anti-spike-RBD-IgG and T-cell response were linked at both time points (all groups combined). All regimes yielded neutralizing antibodies and increased antibody avidity at T2.
Interdependencies between humoral and cellular immune responses differ between common SARS-CoV-2 vaccination regimes. T-cell activation is unlikely to compensate for poor humoral responses.
同源和异源 SARS-CoV-2 疫苗可产生不同的刺突蛋白定向体液和细胞免疫应答。本研究旨在探索它们目前未知的相互依存关系。
COV-ADAPT 是一项前瞻性、观察性队列研究，纳入了 417 名接受同源 ChAdOx1 nCoV-19、同源 BNT162b2 或异源 ChAdOx1 nCoV-19/BNT162b2 疫苗接种的医护人员。我们在二次免疫接种前 2 周（T1）和接种后 2-12 周（T2）评估了血液样本中的体液（抗刺突-RBD-IgG、中和抗体和亲和力）和细胞（刺突诱导的 T 细胞干扰素-γ释放）免疫应答。
T1 时，ChAdOx1 nCoV-19 初始接种产生的抗刺突-RBD-IgG 低于 BNT162b2（70±114 vs. 226±279 BAU/ml，p<0.01）。T2 时，BNT162b2 的加强接种优于 ChAdOx1 nCoV-19（抗刺突-RBD-IgG：ChAdOx1 nCoV-19/BNT162b2 2387±1627 和同源 BNT162b2 3202±2184 vs. 同源 ChAdOx1 nCoV-19 413±461 BAU/ml，均 p<0.001；刺突诱导的 T 细胞干扰素-γ释放：ChAdOx1 nCoV-19/BNT162b2 5069±6733 和同源 BNT162b2 4880±7570 vs. 同源 ChAdOx1 nCoV-19 1152±2243 mIU/ml，均 p<0.001）。T2 时，BNT162b2 加强接种组之间未检测到显著差异。对于 ChAdOx1 nCoV-19，未观察到 T 细胞激活的增强作用。我们发现 T1 到 T2 时，抗刺突-RBD-IgG 水平（ChAdOx1 nCoV-19/BNT162b2 和同源 BNT162b2）和 T 细胞反应（同源 ChAdOx1 nCoV-19 和 ChAdOx1 nCoV-19/BNT162b2）之间存在关联。此外，在两个时间点（所有组合并），抗刺突-RBD-IgG 和 T 细胞反应都有关联。所有方案均在 T2 时产生中和抗体并增加抗体亲和力。
常见 SARS-CoV-2 疫苗接种方案之间的体液和细胞免疫应答存在相互依存关系。T 细胞激活不太可能弥补体液免疫应答不佳的情况。
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