A potential broad-spectrum live-attenuated SARS-CoV-2 vaccine derived from pangolin coronavirus and insights into the immune evasion mechanisms of XBB.1.16 variant DOI Creative Commons
Lihua Song, Shanshan Lu,

Shengdong Luo

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 5, 2023

Abstract Harnessing SARS-CoV-2 related viruses from wild animals for live vaccines is an underexplored but promising approach, akin to the vaccinia virus used against smallpox. This study evaluated potential of a live-attenuated vaccine derived pangolin coronavirus GX_P2V. We observed that attenuated mutant, GX_P2V(short_3UTR), conferred significant and long-lasting protection in golden hamsters, particularly after two doses. Furthermore, we show sera vaccinated convalescents variant XBB.1.16 exhibited high titers neutralizing antibody suggesting GX_P2V(short_3UTR) shares epitopes with XBB.1.16. also same displayed significantly reduced itself, decoy-like immune evasion strategy high-level cross-neutralizing antibodies induced by highly immunogenic may not be able efficiently neutralize itself. Our findings emphasize GX_P2V(short_3UTR)'s as broad-spectrum shed light on novel mechanisms variant.

Language: Английский

Monoclonal antibody therapies against SARS-CoV-2 DOI Open Access
Daniele Focosi, Scott A. McConnell, Arturo Casadevall

et al.

The Lancet Infectious Diseases, Journal Year: 2022, Volume and Issue: 22(11), P. e311 - e326

Published: July 5, 2022

Language: Английский

Citations

214
Evolution of the SARS-CoV-2 Omicron spike DOI Creative Commons
Ruth Parsons, Priyamvada Acharya

Cell Reports, Journal Year: 2023, Volume and Issue: 42(12), P. 113444 - 113444

Published: Nov. 18, 2023

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern, first identified in November 2021, rapidly spread worldwide and diversified into several subvariants. spike (S) protein accumulated an unprecedented number sequence changes relative to previous variants. In this review, we discuss how S structural features modulate host cell receptor binding, virus entry, immune evasion highlight these differentiate from We also examine key properties track across the still-evolving subvariants importance continuing surveillance evolution over time.

Language: Английский

Citations

35
Defining a de novo non-RBM antibody as RBD-8 and its synergistic rescue of immune-evaded antibodies to neutralize Omicron SARS-CoV-2 DOI Creative Commons
Xia Rao,

Runchu Zhao,

Zhou Tong

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(52)

Published: Dec. 18, 2023

Currently, monoclonal antibodies (MAbs) targeting the SARS-CoV-2 receptor binding domain (RBD) of spike (S) protein are classified into seven classes based on their epitopes. However, most these seriously impaired by Omicron and its subvariants, especially recent BQ.1.1, XBB derivatives. Identification broadly neutralizing MAbs against currently circulating variants is imperative. In this study, we identified a “breathing” cryptic epitope in S protein, named as RBD-8. Two human MAbs, BIOLS56 IMCAS74, were isolated recognizing with broad neutralization abilities tested sarbecoviruses, including SARS-CoV, pangolin-origin coronaviruses, all (Omicron BA.4/BA.5, subvariants). Searching through literature, some more RBD-8 defined. More importantly, rescues immune-evaded antibody, RBD-5 MAb IMCAS-L4.65, making bispecific MAb, to neutralize BQ.1 thereby producing an cover subvariants. Structural analysis reveals that effect depends extent exposure, which affected angle antibody number up-RBDs induced angiotensin-converting enzyme 2 binding. This recognizes non- motif (non-RBM) provides guidance for development universal therapeutic vaccines COVID-19.

Language: Английский

Citations

19
Defining a highly conserved cryptic epitope for antibody recognition of SARS-CoV-2 variants DOI Creative Commons

Aihua Hao,

Wenping Song, Cheng Li

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: July 8, 2023

Language: Английский

Citations

13
Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes DOI Creative Commons
Xixi Zhang, Zimu Li, Yanjun Zhang

et al.

Life Science Alliance, Journal Year: 2023, Volume and Issue: 6(9), P. e202201796 - e202201796

Published: July 4, 2023

SARS-CoV-2 spike protein (S) is structurally dynamic and has been observed by cryo-EM to adopt a variety of prefusion conformations that can be categorized as locked, closed, open. S-trimers adopting locked are tightly packed featuring structural elements incompatible with RBD in the “up” position. For S, it shown transient under neutral pH. Probably because their transience, remain largely uncharacterized for SARS-CoV-1 S. In this study, we introduced x1, x2, x3 disulfides into Some these have preserve rare when Introduction allowed us image other S cryo-EM. We identified bound cofactors features associated conformations. compare newly determined structures available SARS-related CoVs identify conserved discuss possible functions.

Language: Английский

Citations

11
Potent and broadly neutralizing antibodies against sarbecoviruses elicited by single ancestral SARS-CoV-2 infection DOI Creative Commons
Yu Lei,

Yajie Wang,

Yuanchen Liu

et al.

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 6, 2025

The emergence of various SARS-CoV-2 variants presents challenges for antibody therapeutics, emphasizing the need more potent and broadly neutralizing antibodies. Here, we employed an unbiased screening approach successfully isolated two antibodies from individuals with only exposure to ancestral SARS-CoV-2. One these antibodies, CYFN1006-1, exhibited robust cross-neutralization against a spectrum variants, including latest KP.2, KP.3 XEC, consistent IC50 values ranging ~1 5 ng/mL. It also displayed broad neutralization activity SARS-CoV related sarbecoviruses. Structural analysis revealed that target shared hotspot but mutation-resistant epitopes, their Fabs locking receptor binding domains (RBDs) in "down" conformation through interactions adjacent RBDs, cross-linking Spike trimers into di-trimers. In vivo studies conducted JN.1-infected hamster model validated protective efficacy CYFN1006-1. These findings suggest activities can be identified exclusively virus exposure.

Language: Английский

Citations

0
Mapping the antibody response to Lassa virus vaccination of non-human primates DOI Creative Commons
Adrian Enriquez, Ruben Diaz Avalos, Diptiben Parekh

et al.

EBioMedicine, Journal Year: 2025, Volume and Issue: 114, P. 105673 - 105673

Published: April 1, 2025

Lassa fever, caused by virus, is a severe disease, endemic in Western Africa, for which no vaccines or therapeutics are yet approved. Understanding the immune responses elicited candidate key approval, including characterisation of antibody epitopes recognised and capacity neutralisation. Here we used negative-stain electron microscopy polyclonal epitope mapping (EMPEM), in-vitro pseudovirus neutralisation assays, biophysical competition assays to uncover components nonhuman primates 26 days after receipt single immunisation with fully protective, recombinant, replication-competent vesicular stomatitis virus-based vaccine bearing virus glycoprotein GPC. Although vaccinee sera overall poorly-neutralising, do directly visualise, within pool, antibodies targeting on GPC that consistent neutralisation, as well known neutralising mAbs. Nearly every animal, example, produced compete mAbs against GP1-A GPC-A epitopes. The most abundant classes antibodies, however, directed interior interfaces GPC, while other recognise post-fusion not It may be some individual pool neutralising, but abundance non-neutralising reduces potency measured at level. finding, neutralisation-consistent sites important steps design toward eliciting more potent A complete list funding bodies supported this study presented Funding section.

Language: Английский

Citations

0
Structural understanding of SARS-CoV-2 virus entry to host cells DOI Creative Commons

Kim Le,

Shrute Kannappan, Truc Kim

et al.

Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10

Published: Nov. 2, 2023

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major global health concern associated with millions of fatalities worldwide. Mutant variants virus have further exacerbated COVID-19 mortality and infection rates, emphasizing urgent need for effective preventive strategies. Understanding viral mechanism crucial developing therapeutics vaccines. The entry SARS-CoV-2 into host cells key step in pathway has been targeted drug development. Despite numerous reviews virus, there lack comprehensive focusing on structural aspects entry. In this review, we analyze changes Spike proteins during process, dividing process prebinding, receptor binding, proteolytic cleavage, membrane fusion steps. By understanding atomic-scale details entry, can better target intervention We also examine impacts mutations proteins, including Omicron variant, Structural information provides insights effects guide development Finally, discuss available structure-based approaches Overall, review detailed analysis highlighting its significance vaccines against COVID-19. Therefore, our emphasizes importance combating infection.

Language: Английский

Citations

10
Distinct Conformations of SARS-CoV-2 Omicron Spike Protein and Its Interaction with ACE2 and Antibody DOI Open Access
Myeongsang Lee, Marian Major, Huixiao Hong

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3774 - 3774

Published: Feb. 14, 2023

Since November 2021, Omicron has been the dominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant that causes disease 2019 (COVID-19) and continuously impacted human health. sublineages are still increasing cause increased transmission infection rates. The additional 15 mutations on receptor binding domain (RBD) of spike proteins change protein conformation, enabling to evade neutralizing antibodies. For this reason, many efforts have made design new antigenic variants induce effective antibodies in SARS-CoV-2 vaccine development. However, understanding different states with without external molecules not yet addressed. In review, we analyze structures presence absence angiotensin-converting enzyme (ACE2) Compared previously determined for wildtype other such as alpha, beta, delta, gamma, adopts a partially open form. open-form one RBD up is dominant, followed by two up, closed-form down. It suggested competition between ACE2 induces interactions adjacent RBDs protein, which lead form protein. comprehensive structural information could be helpful efficient vaccines against variant.

Language: Английский

Citations

9
Broadly neutralizing antibodies targeting a conserved silent face of spike RBD resist extreme SARS-CoV-2 antigenic drift DOI Creative Commons
Ge Song, Meng Yuan,

Hejun Liu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: April 27, 2023

Developing broad coronavirus vaccines requires identifying and understanding the molecular basis of broadly neutralizing antibody (bnAb) spike sites. In our previous work, we identified sarbecovirus RBD group 1 2 bnAbs. We have now shown that many these bnAbs can still neutralize highly mutated SARS-CoV-2 variants, including XBB.1.5. Structural studies revealed use recurrent germline-encoded CDRH3 features to interact with a conserved region overlaps class 4 bnAb site. Group recognize less well-characterized "site V" on destabilize trimer. The site V has remained largely unchanged in variants is across diverse sarbecoviruses, making it promising target for vaccine development. Our findings suggest targeted strategies may be needed induce effective B cell responses escape resistant subdominant

Language: Английский

Citations

9