SARS-CoV-2 Vaccine-Elicited Immunity after B Cell Depletion in Multiple Sclerosis.

Q3 Medicine ImmunoHorizons Pub Date : 2024-03-01 DOI:10.4049/immunohorizons.2300108
Ryan M Baxter, Berenice Cabrera-Martinez, Tusharkanti Ghosh, Cody Rester, Miguel Guerrero Moreno, Tyler L Borko, Sean Selva, Chelsie L Fleischer, Nicola Haakonsen, Ariana Mayher, Emily Bowhay, Courtney Evans, Todd M Miller, Leah Huey, Jennifer McWilliams, Adrie van Bokhoven, Kevin D Deane, Vijaya Knight, Kimberly R Jordan, Debashis Ghosh, Jared Klarquist, Ross M Kedl, Amanda L Piquet, Elena W Y Hsieh
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Abstract

The impact of B cell deficiency on the humoral and cellular responses to SARS-CoV2 mRNA vaccination remains a challenging and significant clinical management question. We evaluated vaccine-elicited serological and cellular responses in 1) healthy individuals who were pre-exposed to SARS-CoV-2 (n = 21), 2) healthy individuals who received a homologous booster (mRNA, n = 19; or Novavax, n = 19), and 3) persons with multiple sclerosis on B cell depletion therapy (MS-αCD20) receiving mRNA homologous boosting (n = 36). Pre-exposure increased humoral and CD4 T cellular responses in immunocompetent individuals. Novavax homologous boosting induced a significantly more robust serological response than mRNA boosting. MS-α CD20 had an intact IgA mucosal response and an enhanced CD8 T cell response to mRNA boosting compared with immunocompetent individuals. This enhanced cellular response was characterized by the expansion of only effector, not memory, T cells. The enhancement of CD8 T cells in the setting of B cell depletion suggests a regulatory mechanism between B and CD8 T cell vaccine responses.

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多发性硬化症 B 细胞耗竭后 SARS-CoV-2 疫苗激发的免疫力
B 细胞缺乏对接种 SARS-CoV2 mRNA 疫苗后体液和细胞反应的影响仍然是一个具有挑战性的重要临床管理问题。我们评估了疫苗引起的血清学和细胞反应:1)预先暴露于 SARS-CoV-2 的健康人(n = 21);2)接种同源加强剂(mRNA,n = 19;或 Novavax,n = 19)的健康人;3)接受 B 细胞耗竭疗法(MS-αCD20)的多发性硬化症患者,接种 mRNA 同源加强剂(n = 36)。在免疫功能正常的个体中,预暴露可增加体液和 CD4 T 细胞反应。与 mRNA 同源增强相比,Novavax 同源增强诱导的血清反应明显更强。与免疫功能正常的人相比,MS-α CD20 对 mRNA 增强具有完整的 IgA 粘膜反应和增强的 CD8 T 细胞反应。这种增强的细胞反应的特点是只扩增效应T细胞,而不是记忆T细胞。在 B 细胞耗竭的情况下 CD8 T 细胞的增强表明 B 细胞和 CD8 T 细胞疫苗反应之间存在一种调节机制。
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