Nucleic acid delivery of immune-focused SARS-CoV-2 nanoparticles drives rapid and potent immunogenicity capable of single-dose protection

被引：19

作者：

Konrath, Kylie M. ^{[1
,2
]}

Liaw, Kevin ^{[1
]}

Wu, Yuanhan ^{[1
]}

Zhu, Xizhou ^{[1
]}

Walker, Susanne N. ^{[1
]}

Xu, Ziyang ^{[1
,2
]}

Schultheis, Katherine ^{[3
]}

Chokkalingam, Neethu ^{[1
]}

Chawla, Himanshi ^{[4
]}

Du, Jianqiu ^{[5
]}

Tursi, Nicholas J. ^{[1
]}

Moore, Alan ^{[5
]}

Adolf-Bryfogle, Jared ^{[6
]}

Purwar, Mansi ^{[1
]}

Reuschel, Emma L. ^{[1
]}

Frase, Drew ^{[1
]}

Sullivan, Matthew ^{[2
]}

Fry, Benjamin ^{[1
]}

Maricic, Igor ^{[3
]}

Andrade, Viviane M. ^{[3
]}

Iffland, Christel ^{[7
]}

Crispin, Max ^{[4
]}

Broderick, Kate E. ^{[3
]}

Humeau, Laurent M. P. F. ^{[3
]}

Patel, Ami ^{[1
]}

Smith, Trevor R. F. ^{[3
]}

Pallesen, Jesper ^{[6
]}

Weiner, David B. ^{[1
]}

Kulp, Daniel W. ^{[1
,2
]}

机构：

[1] Wistar Inst Anat & Biol, Vaccine & Immunotherapy Ctr, Philadelphia, PA 19104 USA

[2] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA

[3] Inovio Pharmaceut, Plymouth Meeting, PA 19462 USA

[4] Univ Southampton, Sch Biol Sci, Southampton SO17 1BJ, Hants, England

[5] Indiana Univ, Mol & Cellular Biochem, Bloomington, IN 47405 USA

[6] Inst Prot Innovat, Boston, MA 02115 USA

[7] Ligand Pharmaceut Inc, San Diego, CA 92121 USA

来源：

CELL REPORTS | 2022年 / 38卷 / 05期

关键词：

RECEPTOR-BINDING DOMAIN; NEUTRALIZING ANTIBODIES; HEMAGGLUTININ-STEM; VACCINES; PROTEIN; VIRUS; INFECTION; RESPONSES; DESIGN; SITE;

D O I：

10.1016/j.celrep.2022.110318

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may target epitopes that reduce durability or increase the potential for escape from vaccine-induced immunity. Using synthetic vaccinology, we have developed rationally immune-focused SARS-CoV-2 Spike-based vaccines. Glycans can be employed to alter antibody responses to infection and vaccines. Utilizing computational modeling and in vitro screening, we have incorporated glycans into the receptor-binding domain (RBD) and assessed antigenic profiles. We demonstrate that glycan-coated RBD immunogens elicit stronger neutralizing antibodies and have engineered seven multivalent configurations. Advanced DNA delivery of engineered nanoparticle vaccines rapidly elicits potent neutralizing antibodies in guinea pigs, hamsters, and multiple mouse models, including human ACE2 and human antibody repertoire transgenics. RBD nanoparticles induce high levels of cross-neutralizing antibodies against variants of concern with durable titers beyond 6 months. Single, low-dose immunization protects against a lethal SARS-CoV-2 challenge. Single-dose coronavirus vaccines via DNA-launched nanoparticles provide a platform for rapid clinical translation of potent and durable coronavirus vaccines.

引用

页数：26

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