SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination.
SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination.
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DOI：
10.1016/j.ebiom.2022.104402
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发表时间：
2023-01
期刊：
影响因子：
11.1
通讯作者：
Openshaw, Peter J. M.
中科院分区：
文献类型：
--
作者：
Liew, Felicity;Talwar, Shubha;Cross, Andy;Willett, Brian J.;Scott, Sam;Logan, Nicola;Siggins, Matthew K.;Swieboda, Dawid;Sidhu, Jasmin K.;Efstathiou, Claudia;Moore, Shona C.;Davis, Chris;Mohamed, Noura;Nunag, Jose;King, Clara;Thompson, A. A. Roger;Rowland-Jones, Sarah L.;Docherty, Annemarie B.;Chalmers, James D.;Ho, Ling-Pei;Horsley, Alexander;Raman, Betty;Poinasamy, Krisnah;Marks, Michael;Kon, Onn Min;Howard, Luke;Wootton, Daniel G.;Dunachie, Susanna;Quint, Jennifer K.;Evans, Rachael A.;V. Wain, Louise;Fontanella, Sara;Silva, Thushan I. de;Ho, Antonia;Harrison, Ewen;Baillie, J. Kenneth;Semple, Malcolm G.;Brightling, Christopher;Thwaites, Ryan S.;Turtle, Lance;Openshaw, Peter J. M.
关键词：
对SARS-CoV-2免疫的大多数研究集中在循环抗体上，对阻止病毒复制和向前传播的粘膜防御的了解有限。我们研究了因COVID-19住院一年后的鼻和血浆抗体反应，包括引入SARS-CoV-2疫苗接种的时期。在这项随访研究中，通过ISARIC 4C和PHOSP-COVID联盟，从2020年2月至2021年3月期间因COVID-19住院的446名成年人中前瞻性收集了血浆和鼻吸附样本。通过电化学发光法测定了对祖先SARS-CoV-2、Delta和Omicron（BA.1）变体的NP和S的IgA和IgG反应，并与血浆中和数据进行了比较。证明了强且一致的鼻抗NP和抗S伊加应答，其在9个月内保持升高（p < 0.0001）。鼻和血浆抗S IgG保持升高至少12个月（p < 0.0001），与对照组相比，血浆中和滴度针对所有变体均升高（p < 0.0001）。在有完整数据的323人中，307人在6至12个月之间接种了疫苗;与所有SARS-CoV-2变体的鼻和血浆伊加和IgG抗S滴度的升高一致，尽管鼻伊加的变化很小（10个月后变化1.46倍，p = 0.011），中位数仍低于流行前对照确定的阳性阈值。入院后12个月的样本显示鼻伊加和血浆IgG抗S应答之间无相关性（R = 0.05，p = 0.18），表明鼻伊加应答与血浆中的应答不同，并且通过疫苗接种最小程度地增强。感染后9个月鼻腔伊加反应下降，随后接种疫苗的影响很小，这可能解释了缺乏持久的鼻腔防御再感染和接种疫苗对传播的影响有限。这些发现强调了开发增强鼻腔免疫力的疫苗的必要性。这项研究得到了ISARIC 4C和PHOSP-COVID财团的支持。ISARIC 4C由和的赠款支持。利物浦实验癌症医学中心为这项研究提供了基础设施支持。PHOSP-COVD研究由和共同资助。资助者不参与研究设计、数据解释或本手稿的撰写。
Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the and the . Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by and . The funders were not involved in the study design, interpretation of data or the writing of this manuscript.
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