T-cell and antibody responses to first BNT162b2 vaccine dose in previously infected and SARS-CoV-2-naive UK health-care workers: a multicentre prospective cohort study.
T-cell and antibody responses to first BNT162b2 vaccine dose in previously infected and SARS-CoV-2-naive UK health-care workers: a multicentre prospective cohort study.
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DOI：
10.1016/s2666-5247(21)00275-5
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发表时间：
2022-01
期刊：
影响因子：
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通讯作者：
PITCH Consortium
中科院分区：
文献类型：
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作者：
Angyal A;Longet S;Moore SC;Payne RP;Harding A;Tipton T;Rongkard P;Ali M;Hering LM;Meardon N;Austin J;Brown R;Skelly D;Gillson N;Dobson SL;Cross A;Sandhar G;Kilby JA;Tyerman JK;Nicols AR;Spegarova JS;Mehta H;Hornsby H;Whitham R;Conlon CP;Jeffery K;Goulder P;Frater J;Dold C;Pace M;Ogbe A;Brown H;Ansari MA;Adland E;Brown A;Chand M;Shields A;Matthews PC;Hopkins S;Hall V;James W;Rowland-Jones SL;Klenerman P;Dunachie S;Richter A;Duncan CJA;Barnes E;Carroll M;Turtle L;de Silva TI;PITCH Consortium
以前感染过SARS-CoV-2会影响对第一剂SARS-CoV-2疫苗的免疫反应。我们的目的是比较有和没有SARS-CoV-2感染史的卫生保健工作者在单剂量BNT162b2 (tozinameran; Pfizer-BioNTech) mRNA疫苗后的SARS-CoV-2特异性t细胞和抗体反应。我们在英国的四个医院（牛津、利物浦、纽卡斯尔和谢菲尔德）对参加PITCH研究的卫生保健工作者进行了抽样。所有同意参加这项前瞻性队列研究的18岁或以上的卫生保健工作者都被纳入，没有适用排除标准。在可能的情况下，在接种前和接种一次或两次（间隔3-4周）BNT162b2疫苗后28（±7）天采集血样。以前的感染是通过记录的sars - cov -2阳性RT-PCR结果或存在阳性的抗sars - cov -2核衣壳抗体来确定的。在分析时可获得样本的所有参与者中，我们测量了峰值特异性IgG抗体，并通过干扰素-γ酶联免疫斑点法定量了t细胞反应，将sars - cov -2初始个体与先前感染的个体进行了比较。在2020年12月9日至2021年2月9日期间，119名sars - cov -2新手和145名先前感染的卫生保健工作者接种了一剂BNT162b2疫苗，25名sars - cov -2新手卫生保健工作者接种了两剂BNT162b2疫苗。在以前感染的卫生保健工作者中，从以前感染到接种疫苗的中位时间为268天（IQR 232-285）。在单次给药后28天（IQR 27-33），以前感染（n=76）的新鲜外周血单个核细胞（PBMCs）中测量的刺突特异性t细胞反应高于未感染（n=45）的卫生保健工作者（中位数为284 [IQR 150-461] vs 55 [IQR 24-132]斑形成单位[sfu] / 106 PBMCs； p< 0.0001）。使用冷冻保存的PBMCs，先前感染个体（n=52）在接受一次疫苗剂量后的t细胞应答与未感染个体（n=19）接受两次疫苗剂量后的t细胞应答相当（中位数为152 [IQR 119-275] vs 162 [104-258] sfu /106 PBMCs， p= 1.00）。142名先前感染的卫生保健工作者单次注射后的抗刺突IgG抗体反应（中位数为270 373 [IQR 203 461-535 188]抗体单位[AU] /mL）高于111名首次感染的卫生保健工作者一次注射后的抗体反应（35 001 [17 099-55 341]AU/mL, p< 0.0001），高于25名首次感染的卫生保健工作者两次注射后的抗体反应（180 904 [108 221-242 467]AU/mL, p< 0.0001）。与初次感染SARS-CoV-2的个体相比，单剂BNT162b2疫苗可能对先前感染过SARS-CoV-2的个体提供更大的保护，包括对相关变体的保护。未来的研究应确定在感染后接种疫苗的个体中，第二剂疫苗对免疫反应的强度和持久性的额外益处，同时评估延长疫苗接种间隔的影响。英国卫生和社会保障部，以及英国冠状病毒免疫学联合会。
Previous infection with SARS-CoV-2 affects the immune response to the first dose of the SARS-CoV-2 vaccine. We aimed to compare SARS-CoV-2-specific T-cell and antibody responses in health-care workers with and without previous SARS-CoV-2 infection following a single dose of the BNT162b2 (tozinameran; Pfizer–BioNTech) mRNA vaccine. We sampled health-care workers enrolled in the PITCH study across four hospital sites in the UK (Oxford, Liverpool, Newcastle, and Sheffield). All health-care workers aged 18 years or older consenting to participate in this prospective cohort study were included, with no exclusion criteria applied. Blood samples were collected where possible before vaccination and 28 (±7) days following one or two doses (given 3–4 weeks apart) of the BNT162b2 vaccine. Previous infection was determined by a documented SARS-CoV-2-positive RT-PCR result or the presence of positive anti-SARS-CoV-2 nucleocapsid antibodies. We measured spike-specific IgG antibodies and quantified T-cell responses by interferon-γ enzyme-linked immunospot assay in all participants where samples were available at the time of analysis, comparing SARS-CoV-2-naive individuals to those with previous infection. Between Dec 9, 2020, and Feb 9, 2021, 119 SARS-CoV-2-naive and 145 previously infected health-care workers received one dose, and 25 SARS-CoV-2-naive health-care workers received two doses, of the BNT162b2 vaccine. In previously infected health-care workers, the median time from previous infection to vaccination was 268 days (IQR 232–285). At 28 days (IQR 27–33) after a single dose, the spike-specific T-cell response measured in fresh peripheral blood mononuclear cells (PBMCs) was higher in previously infected (n=76) than in infection-naive (n=45) health-care workers (median 284 [IQR 150–461] vs 55 [IQR 24–132] spot-forming units [SFUs] per 106 PBMCs; p<0·0001). With cryopreserved PBMCs, the T-cell response in previously infected individuals (n=52) after one vaccine dose was equivalent to that of infection-naive individuals (n=19) after receiving two vaccine doses (median 152 [IQR 119–275] vs 162 [104–258] SFUs/106 PBMCs; p=1·00). Anti-spike IgG antibody responses following a single dose in 142 previously infected health-care workers (median 270 373 [IQR 203 461–535 188] antibody units [AU] per mL) were higher than in 111 infection-naive health-care workers following one dose (35 001 [17 099–55 341] AU/mL; p<0·0001) and higher than in 25 infection-naive individuals given two doses (180 904 [108 221–242 467] AU/mL; p<0·0001). A single dose of the BNT162b2 vaccine is likely to provide greater protection against SARS-CoV-2 infection in individuals with previous SARS-CoV-2 infection, than in SARS-CoV-2-naive individuals, including against variants of concern. Future studies should determine the additional benefit of a second dose on the magnitude and durability of immune responses in individuals vaccinated following infection, alongside evaluation of the impact of extending the interval between vaccine doses. UK Department of Health and Social Care, and UK Coronavirus Immunology Consortium.