Innate Immune Responses of Vaccinees Determine Early Neutralizing Antibody Production After ChAdOx1nCoV-19 Vaccination.
Innate Immune Responses of Vaccinees Determine Early Neutralizing Antibody Production After ChAdOx1nCoV-19 Vaccination.
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DOI：
10.3389/fimmu.2022.807454
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发表时间：
2022
影响因子：
7.3
通讯作者：
Shieh CC
中科院分区：
文献类型：
--
作者：
Shen CF;Yen CL;Fu YC;Cheng CM;Shen TC;Chang PD;Cheng KH;Liu CC;Chang YT;Chen PL;Ko WC;Shieh CC
先天免疫，配备模式识别受体，包括Toll样受体（TLR），是免疫细胞激活和连接到抗微生物的适应性免疫的关键。然而，关于年龄对SARS-CoV 2腺病毒载体疫苗应答的先天免疫的影响及其与特异性免疫应答的关系的信息仍然很少。在ChAdOx 1 nCoV-19（AZD 1222）疫苗接种前入组了15例25-35岁受试者（年轻组）和5例60-70岁受试者（老年组）。我们在接种前和每次注射后3-5天用流式细胞术测定了用TLR激动剂（对于TLR 3为poly（I：C）;对于TLR 4为LPS;对于TLR 7为咪喹莫特;对于TLR 9为CpG）离体刺激的单核细胞、自然杀伤（NK）细胞和B细胞的活化标志物和细胞因子产生。抗SARS-CoV 2中和抗体滴度（替代病毒中和试验，sVNT）使用第一次接种后2个月和完全接种后1个月收集的血清进行测量。在第一次接种后，年长的成年疫苗接种者比年轻疫苗接种者具有更弱的疫苗诱导的sVNT（47.2±19.3%对21.2± 22.2%，p值<0.05），但在第二次接种后，该差异变得不显著。咪喹莫特、LPS和CpG可显著诱导幼年组IgD+ CD 27- naïve和IgD-CD 27+记忆B细胞中CD 86的表达。相反，在老年组中，只有IgD+ CD 27- naïve B细胞对这些TLR激动剂有反应。咪喹莫德强烈诱导年轻组CD 14+单核细胞中CD 86的表达，但在老年组中则不然。接种后，第1次接种后，年轻组在CD 3-CD 56 dim NK细胞中具有显著更高的IFN-γ表达，而第2次接种后，老年组在CD 56 bright NK细胞中具有显著更高的IFN-γ和颗粒酶B表达（所有p值<0.05）。首次接种后CD 56 dim和CD 56 bright NK细胞中的IFN-γ表达以及LPS和咪喹莫特刺激后CD 14+单核细胞和IgD-CD 27-双阴性B细胞中的CD 86表达与疫苗诱导的抗体应答相关。第一次接种后的先天免疫应答与中和抗体的产生相关。与年轻人相比，老年人通过TLR刺激可能存在先天免疫应答缺陷，接种疫苗后先天免疫激活特征较弱或延迟。
Innate immunity, armed with pattern recognition receptors including Toll-like receptors (TLR), is critical for immune cell activation and the connection to anti-microbial adaptive immunity. However, information regarding the impact of age on the innate immunity in response to SARS-CoV2 adenovirus vector vaccines and its association with specific immune responses remains scarce. Fifteen subjects between 25-35 years (the young group) and five subjects between 60-70 years (the older adult group) were enrolled before ChAdOx1 nCoV-19 (AZD1222) vaccination. We determined activation markers and cytokine production of monocyte, natural killer (NK) cells and B cells ex vivo stimulated with TLR agonist (poly (I:C) for TLR3; LPS for TLR4; imiquimod for TLR7; CpG for TLR9) before vaccination and 3-5 days after each jab with flow cytometry. Anti-SARS-CoV2 neutralization antibody titers (surrogate virus neutralization tests, sVNTs) were measured using serum collected 2 months after the first jab and one month after full vaccination. The older adult vaccinees had weaker vaccine-induced sVNTs than young vaccinees after 1st jab (47.2±19.3% vs. 21.2±22.2%, p value<0.05), but this difference became insignificant after the 2nd jab. Imiquimod, LPS and CpG strongly induced CD86 expression in IgD+CD27- naïve and IgD-CD27+ memory B cells in the young group. In contrast, only the IgD+ CD27- naïve B cells responded to these TLR agonists in the older adult group. Imiquimode strongly induced the CD86 expression in CD14+ monocytes in the young group but not in the older adult group. After vaccination, the young group had significantly higher IFN-γ expression in CD3- CD56dim NK cells after the 1st jab, whilst the older adult group had significantly higher IFN-γ and granzyme B expression in CD56bright NK cells after the 2nd jab (all p value <0.05). The IFN-γ expression in CD56dim and CD56bright NK cells after the first vaccination and CD86 expression in CD14+ monocyte and IgD-CD27-double-negative B cells after LPS and imiquimod stimulation correlated with vaccine-induced antibody responses. The innate immune responses after the first vaccination correlated with the neutralizing antibody production. Older people may have defective innate immune responses by TLR stimulation and weak or delayed innate immune activation profile after vaccination compared with young people.
影响因子：
7
作者：
Lefebvre JS;Haynes L
通讯作者：
Haynes L