A novel STING agonist-adjuvanted pan-sarbecovirus vaccine elicits potent and durable neutralizing antibody and T cell responses in mice, rabbits and NHPs DOI Creative Commons
Zezhong Liu, Jie Zhou, Wei Xu

et al.

Cell Research, Journal Year: 2022, Volume and Issue: 32(3), P. 269 - 287

Published: Jan. 19, 2022

Abstract The emergence of SARS-CoV-2 variants and potentially other highly pathogenic sarbecoviruses in the future highlights need for pan-sarbecovirus vaccines. Here, we discovered a new STING agonist, CF501, found that CF501-adjuvanted RBD-Fc vaccine (CF501/RBD-Fc) elicited significantly stronger neutralizing antibody (nAb) T cell responses than Alum- cGAMP-adjuvanted mice. Vaccination rabbits rhesus macaques (nonhuman primates, NHPs) with CF501/RBD-Fc exceptionally potent nAb against its nine 41 S-mutants, SARS-CoV bat SARSr-CoVs. CF501/RBD-Fc-immunized hACE2-transgenic mice were almost completely protected challenge, even 6 months after initial immunization. NHPs immunized single dose produced high titers nAbs. also exhibited durable humoral cellular immune showed remarkably reduced viral load upper lower airways upon challenge at 108 days post final Thus, can be further developed as novel to combat current outbreaks sarbecovirus diseases.

Language: Английский

Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement DOI Creative Commons
Matthew McCallum,

Nadine Czudnochowski,

Laura E. Rosen

et al.

Science, Journal Year: 2022, Volume and Issue: 375(6583), P. 864 - 868

Published: Feb. 24, 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern evades antibody-mediated immunity that comes from vaccination or infection with earlier variants due to accumulation numerous spike mutations. To understand the antigenic shift, we determined cryo–electron microscopy and x-ray crystal structures protein receptor-binding domain bound broadly neutralizing sarbecovirus monoclonal antibody (mAb) S309 (the parent mAb sotrovimab) human ACE2 receptor. We provide a blueprint for understanding marked reduction binding other therapeutic mAbs leads dampened activity. Remodeling interactions between likely explains enhanced affinity host receptor relative ancestral virus.

Language: Английский

Citations

510
Systems vaccinology of the BNT162b2 mRNA vaccine in humans DOI Open Access
Prabhu S. Arunachalam, Madeleine Scott, Thomas Hagan

et al.

Nature, Journal Year: 2021, Volume and Issue: 596(7872), P. 410 - 416

Published: July 12, 2021

Language: Английский

Citations

461
SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern DOI Creative Commons
Matthew McCallum, Jessica Bassi, Anna De Marco

et al.

Science, Journal Year: 2021, Volume and Issue: 373(6555), P. 648 - 654

Published: July 1, 2021

A novel variant of concern (VOC) named CAL.20C (B.1.427/B.1.429), which was originally detected in California, carries spike glycoprotein mutations S13I the signal peptide, W152C N-terminal domain (NTD), and L452R receptor-binding (RBD). Plasma from individuals vaccinated with a Wuhan-1 isolate-based messenger RNA vaccine or convalescent exhibited neutralizing titers that were reduced 2- to 3.5-fold against B.1.427/B.1.429 relative wild-type pseudoviruses. The mutation activity 14 34 RBD-specific monoclonal antibodies (mAbs). resulted total loss neutralization for 10 NTD-specific mAbs because NTD antigenic supersite remodeled by shift peptide cleavage site formation new disulfide bond, as revealed mass spectrometry structural studies.

Language: Английский

Citations

441
Tackling COVID-19 with neutralizing monoclonal antibodies DOI Creative Commons
Davide Corti, Lisa A. Purcell,

Gyorgy Snell

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(12), P. 3086 - 3108

Published: May 26, 2021

Language: Английский

Citations

374
COVID-19 vaccine development: milestones, lessons and prospects DOI Creative Commons
Maochen Li, Han Wang, Lili Tian

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: May 3, 2022

Abstract With the constantly mutating of SARS-CoV-2 and emergence Variants Concern (VOC), implementation vaccination is critically important. Existing vaccines mainly include inactivated, live attenuated, viral vector, protein subunit, RNA, DNA, virus-like particle (VLP) vaccines. Viral vector vaccines, subunit mRNA may induce additional cellular or humoral immune regulations, including Th cell responses germinal center responses, form relevant memory cells, greatly improving their efficiency. However, some be associated with complications like thrombocytopenia myocarditis, raising concerns about safety these COVID-19 Here, we systemically assess efficacy possible different effects on pregnant women, elderly, people diseases acquired immunodeficiency syndrome (AIDS), transplant recipients, cancer patients. Based current analysis, governments agencies are recommended to continue advance vaccine immunization process. Simultaneously, special attention should paid health status timely treatment complications, development, ensuring lives In addition, available measures such as mix-and-match vaccination, developing new nanoparticle optimizing adjuvant improve could considered.

Language: Английский

Citations

342
Molecular basis of immune evasion by the Delta and Kappa SARS-CoV-2 variants DOI Creative Commons
Matthew McCallum, Alexandra C. Walls, Kaitlin R. Sprouse

et al.

Science, Journal Year: 2021, Volume and Issue: 374(6575), P. 1621 - 1626

Published: Dec. 23, 2021

How the Delta variant evades defenses In course of COVID-19 epidemic, variants severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, some which evade immunity or increase transmission. late 2020, and Kappa were detected, became globally dominant by June 2021. McCallum et al . show that vaccine-elicited serum-neutralizing activity is reduced against these variants. Based on biochemistry structural studies, authors mutations in domain binds ACE2 receptor abrogate binding monoclonal antibodies but do not improve binding, suggesting they emerged escape immune recognition. Remodeling N-terminal allows recognition most neutralizing target it. The work could guide development next-generation vaccines antibody therapies. —VV

Language: Английский

Citations

289
Phase 1 randomized trial of a plant-derived virus-like particle vaccine for COVID-19 DOI Creative Commons
Brian J. Ward,

Philipe Gobeil,

Annie Séguin

et al.

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(6), P. 1071 - 1078

Published: May 18, 2021

Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are being deployed, but the global need greatly exceeds supply, and different formulations might be required for specific populations. Here we report Day 42 interim safety immunogenicity data from an observer-blinded, dose escalation, randomized controlled study of a virus-like particle vaccine candidate produced in plants that displays SARS-CoV-2 spike glycoprotein (CoVLP: NCT04450004 ). The co-primary outcomes were short-term tolerability/safety CoVLP assessed by neutralizing antibody (NAb) cellular responses. Secondary this ongoing include assessments up to 12 months after vaccination. Adults (18-55 years, n = 180) at two sites Quebec, Canada, receive intramuscular doses (3.75 μg, 7.5 15 μg) 21 d apart, alone or adjuvanted with AS03 CpG1018. All well tolerated, adverse events vaccination generally mild moderate, transient highest groups. There was no effect on serum NAbs, titers increased significantly both adjuvants. After second dose, NAbs + groups more than tenfold higher Coronavirus 2019 convalescent sera. Both protein-specific interferon-γ interleukin-4 responses also induced. This pre-specified analysis supports further evaluation candidate.

Language: Английский

Citations

273
Correlates of protection against SARS‐CoV‐2 infection and COVID‐19 disease DOI
David Goldblatt, Galit Alter, Shane Crotty

et al.

Immunological Reviews, Journal Year: 2022, Volume and Issue: 310(1), P. 6 - 26

Published: June 5, 2022

Antibodies against epitopes in S1 give the most accurate CoP infection by SARS-CoV-2 coronavirus. Measurement of those antibodies neutralization or binding assays both have predictive value, with antibody titers giving highest statistical correlation. However, protective functions are multiple. multiple other than influence efficacy. The role cellular responses can be discerned respect to CD4

Language: Английский

Citations

244
The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination DOI Creative Commons
Florian Wimmers, Michele Donato, Alex Kuo

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(15), P. 3915 - 3935.e21

Published: June 25, 2021

Language: Английский

Citations

215
Current approaches of nanomedicines in the market and various stage of clinical translation DOI Creative Commons
Xiaoting Shan,

Xiang Gong,

Jie Li

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 12(7), P. 3028 - 3048

Published: March 1, 2022

Compared with traditional drug therapy, nanomedicines exhibit intriguing biological features to increase therapeutic efficiency, reduce toxicity and achieve targeting delivery. This review provides a snapshot of that have been currently launched or in the clinical trials, which manifests diversified trend carrier types, applied indications mechanisms action. From perspective indications, this article presents an overview applications involving prevention, diagnosis treatment various diseases, include cancer, infections, blood disorders, cardiovascular immuno-associated diseases nervous system etc. Moreover, some considerations perspectives research development facilitate their translations clinic.

Language: Английский

Citations

212