Antibody responses to endemic coronaviruses modulate COVID-19 convalescent plasma functionality

被引：52

作者：

Morgenlander, William R. ^{[1
]}

Henson, Stephanie N. ^{[1
]}

Monaco, Daniel R. ^{[1
]}

Chen, Athena ^{[2
]}

Littlefield, Kirsten ^{[3
]}

Bloch, Evan M. ^{[4
]}

Fujimura, Eric ^{[5
,6
]}

Ruczinski, Ingo ^{[2
]}

Crowley, Andrew R. ^{[6
,7
]}

Natarajan, Harini ^{[6
,7
]}

Butler, Savannah E. ^{[6
,7
]}

Weiner, Joshua A. ^{[8
]}

Li, Mamie Z. ^{[5
,6
]}

Bonny, Tania S. ^{[4
]}

Benner, Sarah E. ^{[4
]}

Balagopal, Ashwin ^{[9
]}

Sullivan, David ^{[3
,9
]}

Shoham, Shmuel ^{[9
]}

Quinn, Thomas C. ^{[9
,10
]}

Eshleman, Susan H. ^{[4
]}

Casadevall, Arturo ^{[3
]}

Redd, Andrew D. ^{[9
,10
]}

Laeyendecker, Oliver ^{[9
,10
]}

Ackerman, Margaret E. ^{[8
]}

Pekosz, Andrew ^{[3
]}

Elledge, Stephen J. ^{[5
,6
]}

Robinson, Matthew ^{[9
]}

Tobian, Aaron A. R. ^{[4
]}

Larman, H. Benjamin ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Pathol, Inst Cell Engn,Div Immunol, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD USA

[4] Johns Hopkins Univ, Sch Med, Dept Pathol, Div Transfus Med, Baltimore, MD 21205 USA

[5] Brigham & Womens Hosp, Howard Hughes Med Inst, Dept Med, Div Genet, Boston, MA 02115 USA

[6] Harvard Med Sch, Dept Genet, Program Virol, Boston, MA 02115 USA

[7] Dartmouth Coll, Geisel Sch Med, Dept Microbiol & Immunol, Hanover, NH 03755 USA

[8] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA

[9] Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA

[10] NIAID, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2021年 / 131卷 / 07期

关键词：

SARS-COV; SARS-COV-2; CELLS;

D O I：

10.1172/JCI146927

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

SARS-CoV-2 (CoV2) antibody therapies, including COVID-19 convalescent plasma (CCP), monoclonal antibodies, and hyperimmune globulin, are among the leading treatments for individuals with early COVID-19 infection. The functionality of convalescent plasma varies greatly, but the association of antibody epitope specificities with plasma functionality remains uncharacterized. We assessed antibody functionality and reactivities to peptides across the CoV2 and the 4 endemic human coronavirus (HCoV) genomes in 126 CCP donations. We found strong correlation between plasma functionality and polyclonal antibody targeting of CoV2 spike protein peptides. Antibody reactivity to many HCoV spike peptides also displayed strong correlation with plasma functionality, including pan-coronavirus cross-reactive epitopes located in a conserved region of the fusion peptide. After accounting for antibody crossreactivity, we identified an association between greater alphacoronavirus NL63 antibody responses and development of highly neutralizing antibodies against CoV2. We also found that plasma preferentially reactive to the CoV2 spike receptor binding domain (RBD), versus the betacoronavirus HKU1 RBD, had higher neutralizing titer. Finally, we developed a 2-peptide serosignature that identifies plasma donations with high anti-spike titer, but that suffer from low neutralizing activity. These results suggest that analysis of coronavirus antibody fine specificities may be useful for selecting desired therapeutics and understanding the complex immune responses elicited by CoV2 infection.

引用

页数：12

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