Nanoparticle-based DNA vaccine protects against SARS-CoV-2 variants in female preclinical models DOI Creative Commons
Lays Cordeiro Guimarães, Pedro Augusto Carvalho Costa, Sérgio Scalzo

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 18, 2024

Abstract A safe and effective vaccine with long-term protection against SARS-CoV-2 variants of concern (VOCs) is a global health priority. Here, we develop lipid nanoparticles (LNPs) to provide delivery plasmid DNA (pDNA) show VOCs in female small animal models. Using library LNPs encapsulating unique barcoded (b-DNA), screen for b-DNA after intramuscular administration. The top-performing are further tested their capacity pDNA uptake antigen-presenting cells vitro. lead LNP used encapsulate encoding the HexaPro version spike (LNP-HPS) immunogenicity vivo. LNP-HPS elicit robust protective effect Gamma (P.1), correlating reduced lethality, decreased viral load lungs lung damage. induce potent humoral T cell responses P.1, generate high levels neutralizing antibodies P.1 Omicron (B.1.1.529). Our findings indicate that efficacy elicited by comparable those achieved approved COVID-19 from Biontech/Pfizer Together, these suggest hold great promise as candidate VOCs.

Language: Английский

SARS-CoV-2 variant biology: immune escape, transmission and fitness DOI Creative Commons
Alessandro M. Carabelli, Thomas P. Peacock, Lucy Thorne

et al.

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 18, 2023

In late 2020, after circulating for almost a year in the human population, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibited major step change its adaptation to humans. These highly mutated forms of SARS-CoV-2 had enhanced rates transmission relative previous variants and were termed 'variants concern' (VOCs). Designated Alpha, Beta, Gamma, Delta Omicron, VOCs emerged independently from one another, turn each rapidly became dominant, regionally or globally, outcompeting variants. The success VOC previously dominant variant was enabled by altered intrinsic functional properties virus and, various degrees, changes antigenicity conferring ability evade primed immune response. increased fitness associated with is result complex interplay biology context changing immunity due both vaccination prior infection. this Review, we summarize literature on transmissibility variants, role mutations at furin spike cleavage site non-spike proteins, potential importance recombination success, evolution T cells, innate population immunity. shows complicated relationship among antigenicity, virulence, which has unpredictable implications future trajectory disease burden COVID-19.

Language: Английский

Citations

989
SARS-CoV-2 Omicron variant: recent progress and future perspectives DOI Creative Commons
Yao Fan, Xiang Li, Lei Zhang

et al.

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

Published: April 28, 2022

Abstract Since the outbreak of coronavirus disease 2019 (COVID-19) pandemic, there have been a few variants severe acute respiratory syndrome 2 (SARS-CoV-2), one which is Omicron variant (B.1.1.529). The most mutated SARS-CoV-2 variant, and its high transmissibility immune evasion ability raised global concerns. Owing to enhanced transmissibility, has rapidly replaced Delta as dominant in several regions. However, recent studies shown that exhibits reduced pathogenicity due altered cell tropism. In addition, significant resistance neutralizing activity vaccines, convalescent serum, antibody therapies. present review, advances molecular clinical characteristics infectivity, pathogenicity, was summarized, potential therapeutic applications response infection were discussed. Furthermore, we highlighted future waves strategies end pandemic.

Language: Английский

Citations

479
Innate immune evasion strategies of SARS-CoV-2 DOI Open Access
Judith M. Minkoff, Benjamin R. tenOever

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 11, 2023

Language: Английский

Citations

165
The development of COVID-19 treatment DOI Creative Commons

Yongliang Yuan,

Baihai Jiao, Lili Qu

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Jan. 26, 2023

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a pandemic named disease 2019 (COVID-19) that has become the greatest worldwide public health threat this century. Recent studies have unraveled numerous mysteries SARS-CoV-2 pathogenesis and thus largely improved COVID-19 vaccines therapeutic strategies. However, important questions remain regarding its therapy. In review, recent research advances on mechanism are quickly summarized. We mainly discuss current therapy strategies for COVID-19, with an emphasis antiviral agents, neutralizing antibody therapies, Janus kinase inhibitors, steroids. When necessary, specific mechanisms history present, representative described in detail. Finally, we key outstanding future directions development treatment.

Language: Английский

Citations

164
T Cell Responses to SARS-CoV-2 DOI
Alessandro Sette, John Sidney, Shane Crotty

et al.

Annual Review of Immunology, Journal Year: 2023, Volume and Issue: 41(1), P. 343 - 373

Published: Feb. 8, 2023

A large body of evidence generated in the last two and a half years addresses roles T cells SARS-CoV-2 infection following vaccination. Infection or vaccination induces multi-epitope CD4 CD8 cell responses with polyfunctionality. Early have been associated mild COVID-19 outcomes. In concert animal model data, these results suggest that while antibody are key to prevent infection, may also play valuable reducing disease severity controlling infection. memory after is sustained for at least six months. While neutralizing impacted by variants, most preserved. This review highlights extensive progress made, data knowledge gaps remain, our understanding vaccines.

Language: Английский

Citations

122
SARS‐CoV‐2 variants and vulnerability at the global level DOI Creative Commons
Vivek P. Chavda, Aayushi Patel, Darsh D. Vaghasiya

et al.

Journal of Medical Virology, Journal Year: 2022, Volume and Issue: 94(7), P. 2986 - 3005

Published: March 12, 2022

Numerous variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have evolved. Viral may evolve with harmful susceptibility to immunity established existing COVID-19 vaccination. These are more transmissible, induce relatively extreme illness, evasive immunological features, decrease neutralization using antibodies from vaccinated persons, and susceptible re-infection. The Centers for Disease Control Prevention (CDC) has categorized SARS-CoV-2 mutations as interest (VOI), concern (VOC), high consequence (VOHC). At moment, four VOC many been defined require constant observation. This review article summarizes various surfaced special emphasis on VOCs that spreading across world, well several viral mutational impacts how these modifications alter properties virus.

Language: Английский

Citations

110
Vaccination with SARS-CoV-2 spike protein lacking glycan shields elicits enhanced protective responses in animal models DOI Creative Commons
Han-Yi Huang, Hsin-Yu Liao, Xiaorui Chen

et al.

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(639)

Published: March 1, 2022

A major challenge to end the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is develop a broadly protective vaccine that elicits long-term immunity. As key immunogen, viral surface spike (S) protein frequently mutated, and conserved epitopes are shielded glycans. Here, we revealed S glycosylation has site-differential effects on infectivity. We found generated lung epithelial cells glycoforms associated with increased Compared fully glycosylated protein, immunization of N-glycans trimmed mono-GlcNAc-decorated state (SMG) elicited stronger immune responses better protection for human angiotensin-converting enzyme (hACE2) transgenic mice against variants concern (VOCs). In addition, neutralizing monoclonal antibody was identified from SMG-immunized could neutralize wild-type SARS-CoV-2 VOCs subpicomolar potency. Together, these results demonstrate removal glycan shields expose sequences potential be an effective simple approach developing vaccine.

Language: Английский

Citations

102
SARS-CoV-2-specific T cells in the changing landscape of the COVID-19 pandemic DOI Creative Commons
Antonio Bertoletti, Nina Le Bert, Anthony T. Tan

et al.

Immunity, Journal Year: 2022, Volume and Issue: 55(10), P. 1764 - 1778

Published: Aug. 18, 2022

Language: Английский

Citations

96
Dual spike and nucleocapsid mRNA vaccination confer protection against SARS-CoV-2 Omicron and Delta variants in preclinical models DOI Creative Commons
Renee L. Hajnik, Jessica A. Plante, Yuejin Liang

et al.

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(662)

Published: Sept. 14, 2022

Emergence of SARS-CoV-2 variants concern (VOCs), including the highly transmissible Omicron and Delta strains, has posed constant challenges to current COVID-19 vaccines that principally target viral spike protein (S). Here, we report a nucleoside-modified messenger RNA (mRNA) vaccine expresses more conserved nucleoprotein (mRNA-N) show mRNA-N vaccination alone can induce modest control SARS-CoV-2. Critically, combining with clinically proven S-expressing mRNA (mRNA-S+N) induced robust protection against both variants. In hamster models VOC challenge, demonstrated that, compared mRNA-S alone, combination mRNA-S+N not only in lungs but also provided enhanced upper respiratory tract. vivo CD8

Language: Английский

Citations

95
Impact of antigenic evolution and original antigenic sin on SARS-CoV-2 immunity DOI Creative Commons

Muriel Aguilar-Bretones,

Ron A. M. Fouchier, Marion Koopmans

et al.

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(1)

Published: Jan. 2, 2023

Infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and vaccinations targeting the spike protein (S) offer protective immunity against disease 2019 (COVID-19). This may further be shaped by cross-reactivity common cold coronaviruses. Mutations arising in S that are associated altered intrinsic virus properties immune escape result continued circulation of SARS-CoV-2 variants. Potentially, vaccine updates will required to protect future variants concern, as for influenza. To potent protection variants, these second-generation vaccines need redirect epitopes not merely boost toward conserved domains preimmune individuals. For influenza, efficacy repeated vaccination is hampered original antigenic sin, an attribute memory leads greater induction antibodies specific first-encountered variant immunogen compared subsequent In this Review, recent findings on sin discussed context evolution. Unanswered questions directions highlighted, emphasis impact outcome design.

Language: Английский

Citations

86