概要: SARS-CoV-2 has spread globally and caused the COVID-19 pandemic. Although passively delivered neutralizing antibodies against SARS-CoV-2 are in clinical trials, their mechanism of action in vivo is incompletely understood. Here, we define correlates of protection of neutralizing human monoclonal antibodies (mAbs) in SARS-CoV-2-infected mice. Whereas Fc effector functions are fully dispensable when mAbs are administered as prophylaxis, they are required for optimal protection as therapy. When given after infection, intact but not LALA-PG loss of Fc effector function variant mAbs reduce SARS-CoV-2 burden and lung disease in mice and hamsters. Fc engagement of neutralizing antibodies mitigates inflammation and improves respiratory mechanics, and transcriptional profiling suggests these phenotypes are associated with diminished innate immune signaling and enhanced tissue repair. Immune cell depletions establish that neutralizing mAbs require monocytes for therapeutic efficacy. Our study demonstrates that therapeutic neutralizing mAbs require Fc effector functions to reduce SARS-CoV-2 infection and modulate protective immune responses.
项目整体设计: RNA sequencing analysis was performed with the lung homogenates of naive K18-hACE2 mice or mice infected with SARS-CoV-2 infection at 8 dpi. At 1 (D+1) or 2 (D+2) dpi, mice were given a single 200 ug dose of COV2-2050 or COV2-2050 LALA-PG via an intraperitoneal injection. Note: data for 4 of 6 naive samples were uploaded previously under GSE154104 and labeled as D0 group.
Eight-week-old mice of both sexes were administered 2.5 x 10^4 PFU of SARS-CoV-2 via intranasal administration.
提取方案:
Total RNAs were extracted with the MagMax mirVana Total RNA isolation kit (Thermo Scientific) on the Kingfisher Flex extraction robot (Thermo Scientific).
cDNA libraries were constructed from 10 ng of total RNA from lung tissues of mice. Library construction was performed using 100 ng of cDNA undergoing end repair, A tailing, ligation of universal TruSeq adapters and amplification of 8 cycles to incorporate unique dual index sequences.
建库方案:
Libraries were sequenced on the NovaSeq 6000 (Illumina, San Diego, CA) targeting 40 million read pairs and extending 150 cycles with paired end reads.
测序信息
分子类型:
total RNA
库的片段类型:
PAIRED
库的链类型:
-
测序平台:
ILLUMINA
测序仪型号:
Illumina NovaSeq 6000
链特异性:
unspecific
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文章
Characterization of the SARS-CoV-2 Host Response in Primary Human Airway Epithelial Cells from Aged Individuals.
