针对新冠病毒不同变体诱导产生依赖Fc的功能性抗体，其情况因疫苗类型和既往感染而有所不同。

Induction of Fc-dependent functional antibodies against different variants of SARS-CoV-2 varies by vaccine type and prior infection.

作者信息

Harris Alexander W, Kurtovic Liriye, Nogueira Jeane, Bouzas Isabel, Opi D Herbert, Wines Bruce D, Lee Wen Shi, Hogarth P Mark, Poumbourios Pantelis, Drummer Heidi E, Valim Clarissa, Porto Luís Cristóvão, Beeson James G

机构信息

Burnet Institute, Melbourne, Australia.

Department of Immunology, Monash University, Melbourne, Australia.

出版信息

Commun Med (Lond). 2024 Dec 19;4(1):273. doi: 10.1038/s43856-024-00686-6.

DOI:10.1038/s43856-024-00686-6

PMID:39702507

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11659474/

Abstract

BACKGROUND

SARS-CoV-2 transmission and COVID-19 disease severity is influenced by immunity from natural infection and/or vaccination. Population-level immunity is complicated by the emergence of viral variants. Antibody Fc-dependent effector functions are as important mediators in immunity. However, their induction in populations with diverse infection and/or vaccination histories and against variants remains poorly defined.

METHODS

We evaluated Fc-dependent functional antibodies following vaccination with two widely used vaccines, AstraZeneca (AZ) and Sinovac (SV), including antibody binding of Fcγ-receptors and complement-fixation in vaccinated Brazilian adults (n = 222), some of who were previously infected with SARS-CoV-2, as well as adults with natural infection only (n = 200). IgG, IgM, IgA, and IgG subclasses were also quantified.

RESULTS

AZ induces greater Fcγ-receptor-binding (types I, IIa, and IIIa/b) antibodies than SV or natural infection. Previously infected individuals have significantly greater vaccine-induced responses compared to naïve counterparts. Fcγ-receptor-binding is highest among AZ vaccinated individuals with a prior infection, for all receptor types, and substantial complement-fixing activity is only seen among this group. SV induces higher IgM than AZ, but this does not drive better complement-fixing activity. Some SV responses are associated with subject age, whereas AZ responses are not. Importantly, functional antibody responses are well retained against the Omicron BA.1 S protein, being best retained for Fcγ-receptor-1 binding, and are higher for AZ than SV.

CONCLUSIONS

Hybrid immunity, from combined natural exposure and vaccination, generates strong Fc-mediated antibody functions which may contribute to immunity against evolving SARS-CoV-2 variants. Understanding determinants of Fc-mediated functions may enable future vaccines with greater efficacy against different variants.

摘要

背景

严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的传播以及冠状病毒病2019（COVID-19）的疾病严重程度受自然感染和/或疫苗接种所产生的免疫力影响。病毒变体的出现使群体水平的免疫力变得复杂。抗体Fc依赖性效应功能是免疫中的重要介质。然而，在具有不同感染和/或疫苗接种史的人群中以及针对变体的情况下，它们的诱导情况仍不清楚。

方法

我们评估了接种两种广泛使用的疫苗（阿斯利康（AZ）和科兴（SV））后Fc依赖性功能性抗体，包括在接种疫苗的巴西成年人（n = 222）中Fcγ受体的抗体结合和补体固定情况，其中一些人先前感染过SARS-CoV-2，以及仅自然感染的成年人（n = 200）。还对IgG、IgM、IgA和IgG亚类进行了定量。

结果

与科兴疫苗或自然感染相比，阿斯利康疫苗诱导产生更多的Fcγ受体结合（I型、IIa型和IIIa/b型）抗体。与未感染过的个体相比，先前感染过的个体疫苗诱导的反应明显更强。对于所有受体类型，在先前感染过的接种阿斯利康疫苗的个体中，Fcγ受体结合最高，并且仅在该组中观察到大量补体固定活性。科兴疫苗诱导产生的IgM高于阿斯利康疫苗，但这并未带来更好的补体固定活性。科兴疫苗的一些反应与受试者年龄有关，而阿斯利康疫苗的反应则与年龄无关。重要的是，功能性抗体反应对奥密克戎BA.1刺突蛋白保持良好，对Fcγ受体-1结合的保留效果最佳，并且阿斯利康疫苗诱导产生的功能性抗体反应高于科兴疫苗。