Pre-existing immunity modulates responses to mRNA boosters

被引：21

作者：

Dangi, Tanushree ^{[1
]}

Sanchez, Sarah ^{[1
]}

Lew, Min Han ^{[1
]}

Awakoaiye, Bakare

Visvabharathy, Lavanya ^{[2
]}

Richner, Justin M. ^{[3
]}

Koralnik, Igor J. ^{[2
]}

Penaloza-MacMaster, Pablo ^{[1
]}

机构：

[1] Northwestern Univ, Feinberg Sch Med, Dept Microbiol Immunol, Chicago, IL 60611 USA

[2] Northwestern Univ, Feinberg Sch Med, Ken & Ruth Davee Dept Neurol, Chicago, IL 60611 USA

[3] Univ Illinois, Dept Microbiol & Immunol, Coll Med, Chicago, IL 60612 USA

来源：

CELL REPORTS | 2023年 / 42卷 / 03期

关键词：

T-CELLS; VACCINE; EFFICACY; ANTIBODIES; CAPACITY;

D O I：

10.1016/j.celrep.2023.112167

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

mRNA vaccines are effective in preventing severe COVID-19, but breakthrough infections, emerging variants, and waning immunity warrant the use of boosters. Although mRNA boosters are being implemented, the extent to which pre-existing immunity influences the efficacy of boosters remains unclear. In a cohort of indi-viduals primed with the mRNA-1273 or BNT162b2 vaccines, we report that lower antibody levels before boost are associated with higher fold-increase in antibody levels after boost, suggesting that pre-existing antibody modulates the immunogenicity of mRNA vaccines. Our studies in mice show that pre-existing antibodies accelerate the clearance of vaccine antigen via Fc-dependent mechanisms, limiting the amount of antigen available to prime B cell responses after mRNA boosters. These data demonstrate a "tug of war"between pre-existing antibody responses and de novo B cell responses following mRNA vaccination, and they suggest that transient downmodulation of antibody effector function may improve the efficacy of mRNA boosters.

引用

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