Distinct immune cell dynamics correlate with the immunogenicity and reactogenicity of SARS-CoV-2 mRNA vaccine.

Distinct immune cell dynamics correlate with the immunogenicity and reactogenicity of SARS-CoV-2 mRNA vaccine.
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DOI:
10.1016/j.xcrm.2022.100631
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发表时间:
2022-05-17
影响因子:
14.3
通讯作者:
Takahashi, Yoshimasa
Takahashi, Yoshimasa
中科院分区:
医学1区
文献类型:
--
作者:
Takano, Tomohiro;Morikawa, Miwa;Adachi, Yu;Kabasawa, Kiyomi;Sax, Nicolas;Moriyama, Saya;Sun, Lin;Isogawa, Masanori;Nishiyama, Ayae;Onodera, Taishi;Terahara, Kazutaka;Tonouchi, Keisuke;Nishimura, Masashi;Tomii, Kentaro;Yamashita, Kazuo;Matsumura, Takayuki;Shinkai, Masaharu;Takahashi, Yoshimasa

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两剂Pfizer/BioNTech BNT 162 b2 mRNA疫苗可引发强烈的严重急性呼吸综合征冠状病毒2(SARS-CoV-2)中和抗体,并经常发生不良事件。在这里,通过对92名疫苗接种者进行高维免疫分析,我们确定了六种疫苗诱导的免疫动力学,这些免疫动力学与中和抗体的数量、不良事件的严重程度或两者兼而有之。自然杀伤(NK)/单核细胞亚群(CD 16 + NK细胞、CD 56 high NK细胞和非经典单核细胞)、树突状细胞(DC)亚群(DC 3和CD 11 c − Axl+ Siglec-6+ [AS]-DC)和NKT样细胞的早期动态分别显示为中和抗体滴度、不良事件严重程度和两者的不同细胞相关性。中和抗体或不良事件的细胞相关物始终与干扰素γ(IFN-γ)诱导型趋化因子的升高相关,但趋化因子受体CCR 2和CXCR 3在两种相关物之间以不同的方式表达:疫苗诱导的中和抗体相关物表达和不良事件相关物的组成型表达。这一发现可以指导平衡免疫原性和反应原性的疫苗策略。mRNA疫苗接种者的免疫谱揭示了显著的免疫学变化NK/单核细胞亚群的动力学与中和抗体应答相关树突细胞亚群的动力学与不良事件的严重性相关IFN-γ诱导的趋化因子而不是受体与这些相关性相关。确定SARS-CoV-2 mRNA疫苗接种后中和抗体滴度和全身不良事件的细胞相关性。提出了IFN-γ介导的通路的参与。这些发现为平衡mRNA疫苗的免疫原性和反应原性提供了见解。
Two doses of Pfizer/BioNTech BNT162b2 mRNA vaccine elicit robust severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing antibodies with frequent adverse events. Here, by applying a high-dimensional immune profiling on 92 vaccinees, we identify six vaccine-induced immune dynamics that correlate with the amounts of neutralizing antibodies, the severity of adverse events, or both. The early dynamics of natural killer (NK)/monocyte subsets (CD16+ NK cells, CD56high NK cells, and non-classical monocytes), dendritic cell (DC) subsets (DC3s and CD11c− Axl+ Siglec-6+ [AS]-DCs), and NKT-like cells are revealed as the distinct cell correlates for neutralizing-antibody titers, severity of adverse events, and both, respectively. The cell correlates for neutralizing antibodies or adverse events are consistently associated with elevation of interferon gamma (IFN-γ)-inducible chemokines, but the chemokine receptors CCR2 and CXCR3 are expressed in distinct manners between the two correlates: vaccine-induced expression on the neutralizing-antibody correlate and constitutive expression on the adverse-event correlate. The finding may guide vaccine strategies that balance immunogenicity and reactogenicity. Immune profiling of mRNA vaccinees reveals dramatic immunological changes The dynamics of NK/monocyte subsets correlate with neutralizing-antibody response The dynamics of dendritic cell subsets correlate with severity of adverse events IFN-γ-inducible chemokines, but not the receptors, are related to these correlates Takano et al. identify cellular correlates for neutralizing-antibody titers and systemic adverse events following SARS-CoV-2 mRNA vaccination. The involvement of IFN-γ-mediated pathways is proposed. The findings give insights into balancing the immunogenicity and reactogenicity of mRNA vaccine.
DOI: 10.1084/jem.177.4.1199
发表时间: 1993-04-01
期刊: The Journal of experimental medicine
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发表时间: 1995-07-01
影响因子: 5.4
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DOI: 10.1126/sciimmunol.abi6950
发表时间: 2021-04-15
期刊: Science immunology
影响因子: 24.8
作者:
Goel RR;Apostolidis SA;Painter MM;Mathew D;Pattekar A;Kuthuru O;Gouma S;Hicks P;Meng W;Rosenfeld AM;Dysinger S;Lundgreen KA;Kuri-Cervantes L;Adamski S;Hicks A;Korte S;Oldridge DA;Baxter AE;Giles JR;Weirick ME;McAllister CM;Dougherty J;Long S;D'Andrea K;Hamilton JT;Betts MR;Luning Prak ET;Bates P;Hensley SE;Greenplate AR;Wherry EJ
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mRNA疫苗会诱导SARS-COV-2和关注的变体诱导耐用的免疫记忆。
DOI: 10.1126/science.abm0829
发表时间: 2021-12-03
期刊: Science (New York, N.Y.)
影响因子: --
作者:
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