Delayed boosting improves human antigen-specific Ig and B cell responses to the RH5.1/AS01B malaria vaccine.
Delayed boosting improves human antigen-specific Ig and B cell responses to the RH5.1/AS01B malaria vaccine.
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DOI：
10.1172/jci.insight.163859
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发表时间：
2023-01-24
期刊：
影响因子：
8
通讯作者：
Draper, Simon J.
中科院分区：
文献类型：
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作者：
Nielsen, Carolyn M.;Barrett, Jordan R.;Davis, Christine;Fallon, Jonathan K.;Goh, Cyndi;Michell, Ashlin R.;Griffin, Catherine;Kwok, Andrew;Loos, Carolin;Darko, Samuel;Laboune, Farida;Tekman, Mehmet;Diouf, Ababacar;Miura, Kazutoyo;Francica, Joseph R.;Ransier, Amy;Long, Carole A.;Silk, Sarah E.;Payne, Ruth O.;Minassian, Angela M.;Lauffenburger, Douglas A.;Seder, Robert A.;Douek, Daniel C.;Alter, Galit;Draper, Simon J.
增加血清抗体寿命的疫苗递送的修饰对于最大化功效是非常感兴趣的。我们之前已经证明，与每月给药（0-1-2个月; NCT 02927145）相比，延迟部分（DFx）给药方案（0-1-6个月）-使用AS 01 B佐剂的RH5.1疟疾抗原-大大改善了血清IgG的持久性。然而，尚不清楚DFx给药的潜在机制以及是否存在更广泛的免疫学变化。在这里，通过标准化ELISA、流式细胞术、系统血清学和单细胞RNA-Seq（scRNA-Seq）深入分析了PfRH 5特异性IG和B细胞反应。数据表明，DFx给药增加了循环PfRH 5特异性B细胞和血清IgG 1的数量和持久性。在峰值抗体幅度下，DFx给药通过系统血清学特征集进行区分，包括FcRn结合、IgG亲合力和G2 B和G2 S2 F IgG Fc聚糖比例增加，以及IgG 3、抗体依赖性补体沉积和G1 S1 F IgG Fc聚糖比例降低。同时，scRNA-Seq数据显示来自生殖系的较高CDR 3突变百分比和循环PfRH 5特异性B细胞中浆细胞基因表达降低。因此，我们的数据揭示了DFx给药对体液应答的深刻影响，并提出了可能增强抗体寿命的合理机制，包括血清IG对FcRn结合的改善以及基础细胞应答从循环短寿命浆细胞向非外周长寿命浆细胞的潜在转变。
Modifications to vaccine delivery that increase serum antibody longevity are of great interest for maximizing efficacy. We have previously shown that a delayed fractional (DFx) dosing schedule (0-1-6 month) — using AS01B-adjuvanted RH5.1 malaria antigen — substantially improves serum IgG durability as compared with monthly dosing (0-1-2 month; NCT02927145). However, the underlying mechanism and whether there are wider immunological changes with DFx dosing were unclear. Here, PfRH5-specific Ig and B cell responses were analyzed in depth through standardized ELISAs, flow cytometry, systems serology, and single-cell RNA-Seq (scRNA-Seq). Data indicate that DFx dosing increases the magnitude and durability of circulating PfRH5-specific B cells and serum IgG1. At the peak antibody magnitude, DFx dosing was distinguished by a systems serology feature set comprising increased FcRn binding, IgG avidity, and proportion of G2B and G2S2F IgG Fc glycans, alongside decreased IgG3, antibody-dependent complement deposition, and proportion of G1S1F IgG Fc glycan. Concomitantly, scRNA-Seq data show a higher CDR3 percentage of mutation from germline and decreased plasma cell gene expression in circulating PfRH5-specific B cells. Our data, therefore, reveal a profound impact of DFx dosing on the humoral response and suggest plausible mechanisms that could enhance antibody longevity, including improved FcRn binding by serum Ig and a potential shift in the underlying cellular response from circulating short-lived plasma cells to nonperipheral long-lived plasma cells.
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影响因子：
7.3
作者：
Collins AM;Jackson KJ
通讯作者：
Jackson KJ
让 J 链重新出现在地图上：它的表达如何定义浆细胞的发育？
DOI：
10.4049/jimmunol.1400531
发表时间：
2014-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Castro CD;Flajnik MF
通讯作者：
Flajnik MF
影响因子：
9.2
作者：
Budroni S;Buricchi F;Cavallone A;Bourguignon P;Caubet M;Dewar V;D'Oro U;Finco O;Garçon N;El Idrissi M;Janssens M;Leroux-Roels G;Marchant A;Schwarz T;Van Damme P;Volpini G;van der Most R;Didierlaurent AM;Burny W
通讯作者：
Burny W
影响因子：
64.5
作者：
Chung AW;Kumar MP;Arnold KB;Yu WH;Schoen MK;Dunphy LJ;Suscovich TJ;Frahm N;Linde C;Mahan AE;Hoffner M;Streeck H;Ackerman ME;McElrath MJ;Schuitemaker H;Pau MG;Baden LR;Kim JH;Michael NL;Barouch DH;Lauffenburger DA;Alter G
通讯作者：
Alter G
影响因子：
7
作者：
Crosnier, Cecile;Wanaguru, Madushi;Wright, Gavin J.
通讯作者：
Wright, Gavin J.