Pan Bing-Yi, Tseng IShin, Feng Yen-Chen, Fang Chi-Tai
Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Taiwan Centers for Disease Control, Taipei, Taiwan.
Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
J Formos Med Assoc. 2025 Apr 8. doi: 10.1016/j.jfma.2025.04.002.
An argument against COVID-19 vaccine boosters is that immune imprinting may impair immune responses to new SARS-CoV-2 variants, as some epidemiological studies found a paradoxical increase in Omicron variant infections correlated with the number of prior pre-Omicron vaccine doses. However, substantial variability between studies has left the true impact of boosters uncertain, warranting further investigation.
We systematically reviewed available data and applied meta-regression to identify sources of heterogeneity among studies that examined the impact of pre-Omicron COVID-19 vaccine boosters-compared with primary vaccination series without boosters-on the risk of Omicron variant infections and severe diseases.
We screened 1703 articles and included 35 eligible studies. Heterogeneities in the impact of pre-Omicron boosters on the risk of Omicron infections and severe diseases are attributable to differences in time after boosters, age, and vaccine products (meta-regression R: 70.4 % and 67.7 %, respectively). During the first month post-vaccination, pre-Omicron mRNA boosters decrease-rather than increase-the risk of Omicron infections and severe diseases by 58 % (95 % CI: 54 %-62 %) and 80 % (95 % CI: 68 %-87 %). This effectiveness declines to 9 % (95 % CI: 7 %-23 %) and 55 % (95 % CI: 49 %-60 %) by the sixth and fifth month, respectively. The certainty for evidence is moderate for protection against infections and high for protection against severe diseases.
Our findings refute the immune imprinting hypothesis that COVID-19 boosters impair immunity against new SARS-CoV-2 variants and support current recommendations to stay protected through updated booster vaccination once or twice a year.
反对新冠疫苗加强针的一个观点是，免疫印记可能会损害对新型严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体的免疫反应，因为一些流行病学研究发现，奥密克戎变体感染的反常增加与之前接种奥密克戎之前疫苗剂量的数量相关。然而，研究之间存在很大差异，使得加强针的真正影响尚不确定，需要进一步研究。
我们系统回顾了现有数据，并应用meta回归分析来确定研究之间的异质性来源，这些研究考察了与未接种加强针的初次疫苗接种系列相比，奥密克戎之前的新冠疫苗加强针对奥密克戎变体感染风险和严重疾病的影响。
我们筛选了1703篇文章，纳入了35项符合条件的研究。奥密克戎之前的加强针对奥密克戎感染风险和严重疾病影响的异质性可归因于加强针接种后的时间、年龄和疫苗产品的差异（meta回归R分别为70.4%和67.7%）。在接种疫苗后的第一个月，奥密克戎之前的信使核糖核酸（mRNA）加强针可将奥密克戎感染风险和严重疾病风险降低——而非增加——58%（95%置信区间：54%-62%）和80%（95%置信区间：68%-87%）。到第六个月和第五个月时，这种有效性分别降至9%（95%置信区间：7%-23%）和55%（95%置信区间：49%-60%）。预防感染证据的确定性为中等，预防严重疾病证据的确定性为高。
我们的研究结果驳斥了新冠疫苗加强针会损害对新型SARS-CoV-2变体免疫力的免疫印记假说，并支持目前每年接种一次或两次更新加强针以保持防护的建议。
