Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
Vaccine. 2024 Jul 25;42(19):3953-3960. doi: 10.1016/j.vaccine.2024.05.003. Epub 2024 May 9.
The long-term impact of initial immunogenicity induced by different primary COVID-19 vaccine series remains unclear.
A prospective cohort study was conducted at 10 tertiary hospitals in Korea from March 2021 to September 2022. Immunogenicity assessments included anti-spike protein antibody (Sab), SARS-CoV-2-specific interferon-gamma releasing assay (IGRA), and multiplex cytokine assays for spike protein-stimulated plasma. Spike proteins derived from wild-type SARS-CoV-2 and alpha variant (Spike) and beta and gamma variant (Spike) were utilized.
A total of 235 healthcare workers who had received a two-dose primary vaccine series of either ChAdOx1 or BNT162b2, followed by a third booster dose of BNT162b2 (166 in the ChAdOx1/ChAdOx1/BNT162b2 (CCB) group and 69 in the BNT162b2/BNT162b2/BNT162b2 (BBB) group, based on the vaccine series) were included. Following the primary vaccine series, the BBB group exhibited significantly higher increases in Sab levels, IGRA responses, and multiple cytokines (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, interleukin (IL)-1ra, IFN-γ, IL-2, IL-4, and IL-10) compared to the CCB group (all P < 0.05). One month after the third BNT162b2 booster, the CCB group showed Sab levels comparable to those of the BBB group, and both groups exhibited lower levels after six months without breakthrough infections (BIs). However, among those who experienced BA.1/2 BIs after the third booster, Sab levels increased significantly more in the BBB group than in the CCB group (P < 0.001). IGRA responses to both Spike and Spike proteins were significantly stronger in the BBB group than the CCB group after the third booster, while only the Spike response were higher after BIs (P = 0.007). The BBB group exhibited stronger enhancement of T-cell cytokines (IL-2, IL-4, and IL-17A) after BIs than in the CCB group (P < 0.05).
Differences in immunogenicity induced by the two primary vaccine series persisted, modulated by subsequent booster vaccinations and BIs.
不同初始 COVID-19 疫苗系列诱导的长期免疫原性影响仍不清楚。
本研究在韩国的 10 家三级医院进行了一项前瞻性队列研究，时间为 2021 年 3 月至 2022 年 9 月。免疫原性评估包括抗刺突蛋白抗体（Sab）、SARS-CoV-2 特异性干扰素-γ释放测定（IGRA）和 Spike 蛋白刺激的血浆的多重细胞因子测定。使用源自野生型 SARS-CoV-2 和 alpha 变体（Spike）以及 beta 和 gamma 变体（Spike）的 Spike 蛋白。
共纳入 235 名接受两种初始疫苗系列（ChAdOx1 或 BNT162b2）接种的医护人员，随后接种第三剂 BNT162b2 疫苗（166 名在 ChAdOx1/ChAdOx1/BNT162b2（CCB）组，69 名在 BNT162b2/BNT162b2/BNT162b2（BBB）组，基于疫苗系列）。在初级疫苗系列之后，BBB 组的 Sab 水平、IGRA 反应和多种细胞因子（CCL2/MCP-1、CCL3/MIP-1α、CCL4/MIP-1β、白细胞介素 (IL)-1ra、IFN-γ、IL-2、IL-4 和 IL-10）的增加明显高于 CCB 组（均 P<0.05）。在第三次 BNT162b2 加强针接种后一个月，CCB 组的 Sab 水平与 BBB 组相当，两组在六个月后均无突破性感染（BI）时水平较低。然而，在第三次加强针接种后经历 BA.1/2 BI 的人群中，BBB 组的 Sab 水平显著高于 CCB 组（P<0.001）。在第三次加强针接种后，BBB 组对 Spike 和 Spike 蛋白的 IGRA 反应均明显强于 CCB 组，而仅在 BI 后 Spike 反应更高（P=0.007）。与 CCB 组相比，BBB 组在 BI 后 T 细胞细胞因子（IL-2、IL-4 和 IL-17A）的增强更为明显（P<0.05）。
两种初始疫苗系列诱导的免疫原性差异持续存在，受随后的加强针接种和 BI 调节。
