National Centre for Infectious Diseases, Singapore.
Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
EBioMedicine. 2024 Sep;107:105275. doi: 10.1016/j.ebiom.2024.105275. Epub 2024 Aug 12.
Understanding how SARS-CoV-2 breakthrough infections impacts the breadth of immune responses against existing and pre-emergent SARS-CoV-2 strains is needed to develop an evidence-based long-term immunisation strategy.
We performed a randomised, controlled trial to assess the immunogenicity of homologous (BNT162b2) versus heterologous (mRNA-1273) booster vaccination in 100 BNT162b2-vaccinated infection-naïve individuals enrolled from October 2021. Post hoc analysis was performed to assess the impact of SARS-CoV-2 infection on humoral and cellular immune responses against wild-type SARS-CoV-2 and/or Omicron subvariants.
93 participants completed the study at day 360. 71% (66/93) of participants reported first SARS-CoV-2 Omicron infection by the end of the study with similar proportions of infections between homologous and heterologous booster groups (72.3% [34/47] vs 69.6% [32/46]; p = 0.82). Mean wildtype SARS-CoV-2 anti-S-RBD antibody level was significantly higher in heterologous booster group compared with homologous group at day 180 (14,588 IU/mL; 95% CI, 10,186-20,893 vs 7447 IU/mL; 4646-11,912; p = 0.025). Participants who experienced breakthrough infections during the Omicron BA.1/2 wave had significantly higher anti-S-RBD antibody levels against wildtype SARS-CoV-2 and antibody neutralisation against BA.1 and pre-emergent BA.5 compared with infection-naïve participants. Regardless of hybrid immunity status, wildtype SARS-CoV-2 anti-S-RBD antibody level declined significantly after six months post-booster or post-SARS-CoV-2 infection.
Booster vaccination with mRNA-1273 was associated with significantly higher antibody levels compared with BNT162b2. Antibody responses are narrower and decline faster among uninfected, vaccinated individuals. Boosters may be more effective if administered shortly before infection outbreaks and at least six months after last infection or booster.
Singapore NMRC, USFDA, MRC.
了解 SARS-CoV-2 突破感染如何影响针对现有和新出现的 SARS-CoV-2 株的免疫反应广度，对于制定基于证据的长期免疫策略至关重要。
我们进行了一项随机对照试验，以评估 100 名接种过 BNT162b2 的无感染史的个体中同源（BNT162b2）与异源（mRNA-1273）加强接种的免疫原性，这些个体于 2021 年 10 月入组。事后分析评估了 SARS-CoV-2 感染对针对野生型 SARS-CoV-2 和/或奥密克戎亚变种的体液和细胞免疫反应的影响。
93 名参与者在第 360 天完成了研究。在研究结束时，71%（66/93）的参与者报告了首次 SARS-CoV-2 奥密克戎感染，同源和异源加强组的感染比例相似（72.3%[34/47]与 69.6%[32/46]；p=0.82）。与同源组相比，异源组在第 180 天的野生型 SARS-CoV-2 抗 S-RBD 抗体水平显著更高（14588 IU/ml；95%CI，10186-20893 与 7447 IU/ml；4646-11912；p=0.025）。在奥密克戎 BA.1/2 波期间经历突破感染的参与者对野生型 SARS-CoV-2 的抗 S-RBD 抗体水平以及对 BA.1 和新出现的 BA.5 的抗体中和作用明显高于未感染的参与者。无论混合免疫状态如何，在加强接种或 SARS-CoV-2 感染后 6 个月，野生型 SARS-CoV-2 抗 S-RBD 抗体水平均显著下降。
与 BNT162b2 相比，mRNA-1273 加强接种与更高的抗体水平相关。在未感染、接种过疫苗的个体中，抗体反应更窄，下降更快。如果在感染爆发前和最后一次感染或加强接种后至少 6 个月内进行加强接种，可能会更有效。
新加坡 NMRC、美国 FDA、MRC。
