Mucosal immunity and antibody anergy in COVID-exposed Covishield vaccinees
Mucosal immunity and antibody anergy in COVID-exposed Covishield vaccinees
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接触过 Covishield 疫苗接种者的粘膜免疫和抗体无反应性
DOI：
10.1101/2022.09.06.22279625
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Kannian P
中科院分区：
文献类型：
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作者：
Kannian P
对SARS-CoV 2疫苗接种的粘膜免疫诱导和纵向应答的认识有限。在此，我们测定了三剂Covishield疫苗后的血清/唾液抗体和细胞因子。通过ECLIA和ELISA/细胞因子微珠阵列分别检测了205名医护人员（HCW）首次给药后1个月、第二次给药后1个月、3个月和6个月的血清以及10名HCW第三次给药后1个月、3个月和6个月的配对血清和刺激的全口液（SWMF）中的抗刺突SARS-CoV 2抗体和细胞因子。第二次接种后一个月，未感染新冠病毒组的抗体显着增加（6倍），但之前接触过新冠病毒的人的抗体下降（1.5倍）。在首次给药后一个月，与COVID初治组相比，先前COVID暴露组中的IL-10水平在统计学上更高（p<0.02）。新冠肺炎初治组的突破性感染率为44%，而新冠肺炎暴露组的再感染率为27%（p<0.02）。第一次和第二次给药后1个月的促炎性细胞因子IL- 17/IL-21以及第二次给药后3个月和6个月的记忆性细胞因子IL-7/IL-15极轻微。抗体在第三次给药后1个月增加，并在第三次给药后3个月和6个月下降，与第二次给药后相似。第三次给药后1个月和6个月的配对血清和SWMF缺乏适应性免疫细胞因子表达。血清中IL-8、MCP-1、TNF-α、IL-6、IL-1β等天然免疫细胞因子水平呈下降趋势，而SWMF组则呈持续下降趋势。因此，我们的研究结果表明，第一剂作为抗体加强，而第二剂诱导抗体无反应性在先前COVID暴露组。快速下降的抗体和最小的T细胞细胞因子引起了对它们在随后的病毒暴露中的持久性的担忧。持续的先天性细胞因子从口腔粘膜发出的保证进一步深入的探索。
Knowledge is limited on mucosal immunity induction and longitudinal responses to vaccination against SARS-CoV2. Here, we determined serum/salivary antibodies and cytokines after three Covishield vaccine doses. Sera from 205 healthcare workers (HCWs) one-month after first- dose; one-, three- and six-months after second-dose; paired sera and stimulated whole mouth fluid (SWMF) from 10 HCWs one-, three- and six-months after third-dose were tested for anti- spike SARS-CoV2 antibodies by ECLIA and for cytokines by ELISA/cytokine bead arrays. One-month after second-dose, antibodies had increased significantly (6-fold) in COVID-naïve group, but declined (1.5-fold) in those previously exposed to COVID. At one-month after first- dose, IL-10 levels were statistically higher in the previously COVID-exposed group compared to COVID-naïve group (p<0.02). Breakthrough infections were 44% in COVID-naïve group, while re-infections were 27% in COVID-exposed group (p<0.02). Proinflammatory cytokines–IL- 17/IL-21 at one-month after first- and second-doses, and memory cytokines–IL-7/IL-15 at three- and six-months after second-dose were minimal. Antibodies spiked at one-month after third- dose and declined by three- and six-months after third-dose similar to post-second-dose. Paired sera and SWMF at one- and six-months after third-dose lacked adaptive immunity cytokine expression. Innate immunity cytokines (MIG, MCP-1, IL-8, TNF-α, IL-6, IL-1β) showed a declining trend in serum, but were sustained in SWMF. Thus, our findings suggest that first-dose acts as an antibody boost, while second-dose induces antibody anergy in the previously COVID- exposed group. Rapidly declining antibodies and minimal T cell cytokines raises concerns over their durability in subsequent virus exposures. Sustained innate cytokines emanating from the oral mucosa warrant further in-depth explorations.
影响因子：
120.7
作者：
Stephenson, Kathryn E.;Le Gars, Mathieu;Barouch, Dan H.
通讯作者：
Barouch, Dan H.
COVID 19 疫苗接种：救世主还是毫无根据的依赖？
影响因子：
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作者：
Mohin M. Sakre;S. Agrawal;R. Ravi;Daljit Singh;P. Bharadwaj
通讯作者：
P. Bharadwaj