Fab and Fc contribute to maximal protection against SARS-CoV-2 following NVX-CoV2373 subunit vaccine with Matrix-M vaccination

被引：81

作者：

Gorman, Matthew J. ^{[1
]}

Patel, Nita ^{[2
]}

Guebre-Xabier, Mimi ^{[2
]}

Zhu, Alex L. ^{[1
,3
]}

Atyeo, Caroline ^{[1
]}

Pullen, Krista M. ^{[4
]}

Loos, Carolin ^{[1
,4
]}

Goez-Gazi, Yenny ^{[5
]}

Carrion, Ricardo, Jr. ^{[5
]}

Tian, Jing-Hui ^{[2
]}

Yuan, Dansu ^{[1
]}

Bowman, Kathryn A. ^{[1
]}

Zhou, Bin ^{[2
]}

Maciejewski, Sonia ^{[2
]}

McGrath, Marisa E. ^{[6
]}

Logue, James ^{[6
]}

Frieman, Matthew B. ^{[6
]}

Montefiori, David ^{[7
]}

Mann, Colin ^{[8
]}

Schendel, Sharon ^{[8
]}

Amanat, Fatima ^{[9
]}

Krammer, Florian ^{[9
,10
]}

Saphire, Erica Ollmann ^{[8
]}

Lauffenburger, Douglas A. ^{[4
]}

Greene, Ann M. ^{[2
]}

Portnoff, Alyse D. ^{[2
]}

Massare, Michael J. ^{[2
]}

Ellingsworth, Larry ^{[2
]}

Glenn, Gregory ^{[2
]}

Smith, Gale ^{[2
]}

Alter, Galit ^{[1
]}

机构：

[1] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA

[2] Novavax Inc, 21 Firstfield Rd, Gaithersburg, MD 20878 USA

[3] Univ Duisburg Essen, Virol & Immunol Program, Essen, Germany

[4] MIT, Dept Biol Engn, Cambridge, MA 02139 USA

[5] Texas Biomed Res Inst, 8715 West Mil Dr, San Antonio, TX 78227 USA

[6] Univ Maryland, Sch Med, 685 West Baltimore St, Baltimore, MD 21201 USA

[7] Duke Univ, Dept Surg, Med Ctr, Durham, NC 27710 USA

[8] La Jolla Inst Immunol, La Jolla, CA 92037 USA

[9] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY USA

[10] Icahn Sch Med Mt Sinai, Dept Pathol, New York, NY USA

来源：

CELL REPORTS MEDICINE | 2021年 / 2卷 / 09期

基金：

美国国家科学基金会;

关键词：

RECEPTOR-BINDING DOMAIN; ANTIBODIES; SPIKE; CELLS;

D O I：

10.1016/j.xcrm.2021.100405

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Recently approved vaccines have shown remarkable efficacy in limiting SARS-CoV-2-associated disease. However, with the variety of vaccines, immunization strategies, and waning antibody titers, defining the correlates of immunity across a spectrum of antibody titers is urgently required. Thus, we profiled the humoral immune response in a cohort of non-human primates immunized with a recombinant SARS-CoV-2 spike glycoprotein (NVX-CoV2373) at two doses, administered as a single-or two-dose regimen. Both antigen dose and boosting significantly altered neutralization titers and Fc-effector profiles, driving unique vaccine-induced antibody fingerprints. Combined differences in antibody effector functions and neutralization were associated with distinct levels of protection in the upper and lower respiratory tract. Moreover, NVX-CoV2373 elicited antibodies that functionally targeted emerging SARS-CoV-2 variants. Collectively, the data presented here suggest that a single dose may prevent disease via combined Fc/Fab functions but that two doses may be essential to block further transmission of SARS-CoV-2 and emerging variants.

引用

页数：23

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