B cell somatic hypermutation following COVID-19 vaccination with Ad26.COV2.S

被引：1
|
作者：
Jacob-Dolan, Catherine [1 ,2 ,3 ]
Lifton, Michelle [1 ]
Powers, Olivia C. [1 ]
Miller, Jessica [1 ]
Hachmann, Nicole P. [1 ]
Vu, Mya [2 ]
Surve, Nehalee [1 ]
Mazurek, Camille R. [1 ]
Fisher, Jana L. [1 ]
Rodrigues, Stefanie [1 ]
Patio, Robert C. [1 ]
Anand, Trisha [1 ]
Le Gars, Mathieu [4 ]
Sadoff, Jerald [4 ]
Schmidt, Aaron G. [2 ,3 ]
Barouch, Dan H. [1 ,2 ,3 ]
机构：
[1] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA
[2] MIT & Harvard, Ragon Inst Mass Gen, Cambridge, MA 02139 USA
[3] Harvard Med Sch, Dept Microbiol, Boston, MA 02115 USA
[4] Janssen Vaccines & Prevent BV, Leiden, Netherlands
来源：
ISCIENCE | 2024年 / 27卷 / 05期
关键词：
monoclonal antibodies; long term affinity; AFFINITY MATURATION; NEUTRALIZING ANTIBODIES; TRANSMISSION; DYNAMICS; EFFICACY; POTENCY; ESCAPE; TRIAL;
D O I：
10.1016/j.isci.2024.109716
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
The viral vector -based COVID-19 vaccine Ad26.COV2.S has been recommended by the WHO since 2021 and has been administered to over 200 million people. Prior studies have shown that Ad26.COV2.S induces durable neutralizing antibodies (NAbs) that increase in coverage of variants over time, even in the absence of boosting or infection. Here, we studied humoral responses following Ad26.COV2.S vaccination in individuals enrolled in the initial Phase 1/2a trial of Ad26.COV2.S in 2020. Through 8 months post vaccination, serum NAb responses increased to variants, including B.1.351 (Beta) and B.1.617.2 (Delta), without additional boosting or infection. The level of somatic hypermutation, measured by nucleotide changes in the VDJ region of the heavy and light antibody chains, increased in Spike -specific B cells. Highly mutated mAbs from these sequences neutralized more SARS-CoV-2 variants than less mutated comparators. These findings suggest that the increase in NAb breadth over time following Ad26.COV2.S vaccination is mediated by affinity maturation.
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页数：13
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