Mwimanzi Francis, Lapointe Hope R, Cheung Peter K, Sang Yurou, Yaseen Fatima, Kalikawe Rebecca, Datwani Sneha, Burns Laura, Young Landon, Leung Victor, Ennis Siobhan, Brumme Chanson J, Montaner Julio S G, Dong Winnie, Prystajecky Natalie, Lowe Christopher F, DeMarco Mari L, Holmes Daniel T, Simons Janet, Niikura Masahiro, Romney Marc G, Brumme Zabrina L, Brockman Mark A
Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada.
British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada.
Open Forum Infect Dis. 2023 Feb 9;10(3):ofad073. doi: 10.1093/ofid/ofad073. eCollection 2023 Mar.
Longer-term immune response data after 3 doses of coronavirus disease 2019 (COVID-19) mRNA vaccine remain limited, particularly among older adults and after Omicron breakthrough infection.
We quantified wild-type- and Omicron-specific serum immunoglobulin (Ig)G levels, angiotensin-converting enzyme 2 displacement activities, and live virus neutralization up to 6 months after third dose in 116 adults aged 24-98 years who remained COVID-19 naive or experienced their first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during this time.
Among the 78 participants who remained COVID-19 naive throughout follow up, wild-type- and Omicron-BA.1-specific IgG concentrations were comparable between younger and older adults, although BA.1-specific responses were consistently significantly lower than wild-type-specific responses in both groups. Wild-type- and BA.1-specific IgG concentrations declined at similar rates in COVID-19-naive younger and older adults, with median half-lives ranging from 69 to 78 days. Antiviral antibody functions declined substantially over time in COVID-19-naive individuals, particularly in older adults: by 6 months, BA.1-specific neutralization was undetectable in 96% of older adults, versus 56% of younger adults. Severe acute respiratory syndrome coronavirus 2 infection, experienced by 38 participants, boosted IgG levels and neutralization above those induced by vaccination alone. Nevertheless, BA.1-specific neutralization remained significantly lower than wild-type, with BA.5-specific neutralization lower still. Higher Omicron BA.1-specific neutralization 1 month after third dose was an independent correlate of lower SARS-CoV-2 infection risk.
Results underscore the immune benefits of the third COVID-19 mRNA vaccine dose in adults of all ages and identify vaccine-induced Omicron-specific neutralization as a correlate of protective immunity. Systemic antibody responses and functions however, particularly Omicron-specific neutralization, decline rapidly in COVID-19-naive individuals, particularly in older adults, supporting the need for additional booster doses.
3剂2019冠状病毒病（COVID-19）mRNA疫苗后的长期免疫反应数据仍然有限，尤其是在老年人中以及在奥密克戎突破性感染之后。
我们对116名年龄在24 - 98岁的成年人在第三剂疫苗接种后长达6个月的野生型和奥密克戎特异性血清免疫球蛋白（Ig）G水平、血管紧张素转换酶2置换活性以及活病毒中和能力进行了量化，这些成年人在此期间仍未感染COVID-19或经历了首次严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染。
在整个随访期间仍未感染COVID-19的78名参与者中，年轻和年长成年人的野生型和奥密克戎 - BA.1特异性IgG浓度相当，尽管两组中BA.1特异性反应始终显著低于野生型特异性反应。在未感染COVID-19的年轻和年长成年人中，野生型和BA.1特异性IgG浓度以相似的速率下降，中位半衰期在69至78天之间。在未感染COVID-19的个体中，抗病毒抗体功能随时间大幅下降，尤其是在老年人中：到6个月时，96%的老年人中检测不到BA.1特异性中和作用，而年轻成年人中这一比例为56%。38名参与者经历了SARS-CoV-2感染，这使IgG水平和中和能力提升至高于仅接种疫苗所诱导的水平。然而，BA.1特异性中和作用仍显著低于野生型，BA.5特异性中和作用更低。第三剂疫苗接种后1个月时较高的奥密克戎BA.1特异性中和作用是较低SARS-CoV-2感染风险的独立相关因素。
研究结果强调了第三剂COVID-19 mRNA疫苗对所有年龄段成年人的免疫益处，并确定疫苗诱导的奥密克戎特异性中和作用是保护性免疫的一个相关因素。然而，在未感染COVID-19的个体中，尤其是在老年人中，全身抗体反应和功能，特别是奥密克戎特异性中和作用迅速下降，这支持了需要额外加强接种的必要性。
