Kang Hyunhye, Jung Jin, Ko Geon Young, Lee Jihyun, Oh Eun-Jee
Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Research and Development Institute for In Vitro Diagnostic Medical Devices, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Vaccines (Basel). 2024 Mar 13;12(3):301. doi: 10.3390/vaccines12030301.
The immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) becomes increasingly complex as individuals receive different combinations of vaccine doses and encounter breakthrough infections. Our study focused on the immunogenicity observed over a two-year period in healthy individuals who completed a two-dose series and then experienced booster and/or Omicron infection. In June 2023, we recruited 78 healthcare workers who had previously participated in clinical research initiated in March 2021 at a single medical center in South Korea. At 1, 5, 11, and 25 months after a second dose, we assessed SARS-CoV-2-specific humoral and cellular immune responses. Longitudinal monitoring revealed a significant decline in humoral immunity levels after the second vaccine dose, followed by a substantial increase post-third vaccination or breakthrough infection. In contrast, stable cellular immune responses were consistently observed, with peak humoral and cellular immune measures reached at 25 months after the second dose. Among infection-naïve participants, three-dose vaccinated individuals had decreased neutralizing activity against wild-type (WT) and negative activities against Omicron subvariants BA.2 and BA.4/5, whereas those who received a fourth dose of bivalent BNT had significantly increased neutralizing activity ( < 0.05). All immune metrics tended to increase as the number of vaccine doses increased. Among participants with 4-exposure, homologous vaccination (mRNA × 4) led to higher humoral immunity, whereas heterologous vaccination (ChAd × 2/mRNA × 2) induced stronger cellular responses against multiple SARS-CoV-2 variants by enzyme-linked immunospot assays ( < 0.05). Immune responses from bivalent vaccines or Omicron infection did not show statistically significant differences among exposure number-matched participants ( > 0.05). Omicron exposure significantly increased cross-neutralizing activity, but magnitude of cellular immunity was not significantly altered by Omicron exposure. Our longitudinal study highlights the evolving complexity of SARS-CoV-2 immune responses, showing enhanced immunity with multiple vaccine doses and robust cellular responses from heterologous vaccination. These findings emphasize the need for ongoing surveillance to optimize vaccination strategies against emerging variants.
随着个体接种不同组合的疫苗剂量并遭遇突破性感染，对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的免疫反应变得越来越复杂。我们的研究聚焦于在完成两剂疫苗接种系列后又经历了加强接种和/或奥密克戎感染的健康个体中，在两年时间内观察到的免疫原性。2023年6月，我们招募了78名医护人员，他们此前参与了2021年3月在韩国一家单一医疗中心启动的临床研究。在第二剂疫苗接种后的1、5、11和25个月，我们评估了SARS-CoV-2特异性体液免疫和细胞免疫反应。纵向监测显示，第二剂疫苗接种后体液免疫水平显著下降，随后在第三次接种疫苗或突破性感染后大幅上升。相比之下，细胞免疫反应一直保持稳定，第二剂疫苗接种后25个月时体液免疫和细胞免疫指标达到峰值。在未感染过的参与者中，接种三剂疫苗的个体对野生型（WT）的中和活性降低，对奥密克戎亚型BA.2和BA.4/5的中和活性为阴性，而接受第四剂二价BNT的个体中和活性显著增加（<0.05）。所有免疫指标都倾向于随着疫苗接种剂量的增加而升高。在有4次暴露的参与者中，同源接种（mRNA×4）导致更高的体液免疫，而异源接种（ChAd×2/mRNA×2）通过酶联免疫斑点试验诱导对多种SARS-CoV-2变体更强的细胞反应（<0.05）。在暴露次数匹配的参与者中，二价疫苗或奥密克戎感染引起的免疫反应没有显示出统计学上的显著差异（>0.05）。奥密克戎暴露显著增加了交叉中和活性，但奥密克戎暴露并未显著改变细胞免疫的强度。我们的纵向研究突出了SARS-CoV-2免疫反应不断演变的复杂性，显示了多剂疫苗接种增强了免疫力，以及异源接种产生了强大的细胞反应。这些发现强调了持续监测以优化针对新出现变体的疫苗接种策略的必要性。
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