Continued evasion of neutralizing antibody response by Omicron XBB.1.16

Cell Reports, Journal Year: 2023, Volume and Issue: 42(10), P. 113193 - 113193

Published: Sept. 30, 2023

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to challenge the efficacy vaccination efforts against disease 2019 (COVID-19). Omicron XBB lineage SARS-CoV-2 has presented dramatic evasion neutralizing antibodies stimulated by mRNA and COVID-19 convalescence. XBB.1.16, characterized two mutations relative dominating variant XBB.1.5, i.e., E180V K478R, been on rise globally. In this study, we compare immune escape XBB.1.16 with alongside ancestral variants D614G, BA.2, BA.4/5. We demonstrate that is strongly evasive, extent comparable XBB.1.5 in bivalent-vaccinated healthcare worker sera, 3-dose-vaccinated BA.4/5-wave convalescent sera. Interestingly, spike less fusogenic than phenotype requires both K478R manifest. Overall, our findings emphasize importance continued surveillance need for updated vaccine formulations.

Language: Английский

---

Defining a de novo non-RBM antibody as RBD-8 and its synergistic rescue of immune-evaded antibodies to neutralize Omicron SARS-CoV-2

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

---

Classification of five SARS-CoV-2 serotypes based on RBD antigenicities

Science Bulletin, Journal Year: 2023, Volume and Issue: 68(23), P. 3003 - 3012

Published: Oct. 4, 2023

The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a significant number variants, particularly with the emergence Omicron many sub-variants. These variants have exhibited increased immune escape, leading to reduced efficacy existing vaccines and therapeutic antibodies. Given diminished cross-neutralization observed among these it is plausible that SARS-CoV-2 developed multiple serotypes. As major antigenic site, receptor-binding domain (RBD) viral spike (S) protein was chosen for serotyping. We selected 23 representative including pre-Omicron sub-variants, classified them into five serotypes based on systematic evaluation antigenicities their RBDs. Each serotype includes several genetically distinct variants. Serotype-I encompasses all (with two subtypes), while remaining four are comprised sub-variants at different stages evolution. propose can serve as foundation rapid classification newly emerging guide development future broad-spectrum neutralizing antibodies against disease 2019 (COVID-19).

Language: Английский

---

Breakthrough infection elicits hypermutated IGHV3-53/3-66 public antibodies with broad and potent neutralizing activity against SARS-CoV-2 variants including the emerging EG.5 lineages

PLoS Pathogens, Journal Year: 2023, Volume and Issue: 19(12), P. e1011856 - e1011856

Published: Dec. 4, 2023

The rapid emergence of SARS-CoV-2 variants concern (VOCs) calls for efforts to study broadly neutralizing antibodies elicited by infection or vaccination so as inform the development vaccines and antibody therapeutics with broad protection. Here, we identified two convalescents breakthrough relatively high titers against all tested viruses. Among 50 spike-specific monoclonal (mAbs) cloned from their B cells, top 6 mAbs (KXD01-06) belong previously defined IGHV3-53/3-66 public antibodies. Although most in this class are dramatically escaped VOCs, KXD01-06 exhibit capacity, particularly KXD01-03, which neutralize prototype emerging EG.5.1 FL.1.5.1. Deep mutational scanning reveals that can be current prospective mutations on D420, Y421, L455, F456, N460, A475 N487. Genetic functional analysis further indicates extent somatic hypermutation is critical breadth other Overall, prevalence these provides rationale novel based Meanwhile, developed candidates through affinity maturation.

Language: Английский

---

Spatiotemporal dynamics and epidemiological impact of SARS-CoV-2 XBB lineage dissemination in Brazil in 2023

Microbiology Spectrum, Journal Year: 2024, Volume and Issue: 12(3)

Published: Feb. 5, 2024

ABSTRACT The SARS-CoV-2 XBB is a group of highly immune-evasive lineages the Omicron variant concern that emerged by recombining BA.2-descendent and spread worldwide during 2023. In this study, we combine genomic data ( n = 11,065 sequences) with epidemiological severe acute respiratory infection (SARI) cases collected in Brazil between October 2022 July 2023 to reconstruct space-time dynamics epidemiologic impact dissemination country. Our analyses revealed introduction local emergence carrying convergent mutations within Spike protein, especially F486P, F456L, L455F, propelled XBB* Brazil. average relative instantaneous reproduction numbers + F486P F456L L455F were estimated be 1.24, 1.33, 1.48 higher than other co-circulating (mainly BQ.1*/BE*), respectively. Despite such growth advantage, these had reduced on Brazil’s scenario concerning previous subvariants. peak number SARI from wave was approximately 90%, 80%, 70% lower observed BA.1*, BA.5*, BQ.1* waves, These findings multiple progressively increasing yet relatively limited throughout stand out for their heightened transmissibility, warranting close monitoring months ahead. IMPORTANCE one most affected countries pandemic, more 700,000 deaths mid-2023. This study reconstructs virus country first half 2023, period characterized descendants XBB.1, recombinant BA.2 evolved late 2022. analysis supports marked continuous indigenous bearing similar key sites process followed increments without repercussions incidence cases. Thus, results suggest influenced an intricate interplay factors extend beyond virus's transmissibility alone. also underlines need surveillance allows its ever-shifting composition.

Language: Английский

---

A pan-coronavirus peptide inhibitor prevents SARS-CoV-2 infection in mice by intranasal delivery

Science China Life Sciences, Journal Year: 2023, Volume and Issue: 66(10), P. 2201 - 2213

Published: Aug. 11, 2023

Language: Английский

---

SARS-CoV-2 BA.2.86 (“Pirola”): Is it Pi or Just Another Omicron Sublineage?

Vaccines, Journal Year: 2023, Volume and Issue: 11(11), P. 1634 - 1634

Published: Oct. 25, 2023

The SARS-CoV-2 sublineage BA [...].

Language: Английский

---

SARS-CoV-2 Vaccines: The Advantage of Mucosal Vaccine Delivery and Local Immunity

Vaccines, Journal Year: 2024, Volume and Issue: 12(7), P. 795 - 795

Published: July 18, 2024

Immunity against respiratory pathogens is often short-term, and, consequently, there an unmet need for the effective prevention of such infections. One infectious disease coronavirus 19 (COVID-19), which caused by novel Beta SARS-CoV-2 that emerged around end 2019. The World Health Organization declared illness a pandemic on 11 March 2020, and since then it has killed or sickened millions people globally. development COVID-19 systemic vaccines, impressively led to significant reduction in severity, hospitalization, mortality, contained pandemic’s expansion. However, these vaccines have not been able stop virus from spreading because restricted mucosal immunity. As result, breakthrough infections frequently occurred, new strains emerging. Furthermore, will likely continue circulate like influenza virus, co-exist with humans. upper tract nasal cavity are primary sites infection thus, mucosal/nasal vaccination induce response virus’ transmission warranted. In this review, we present status both approved those under evaluation clinical trials. our approach B-cell peptide-based applied prime-boost schedule elicit

Language: Английский

---

Immune imprinting as a barrier to effective COVID-19 vaccines

Cell Reports Medicine, Journal Year: 2023, Volume and Issue: 4(11), P. 101291 - 101291

Published: Nov. 1, 2023

Wang and colleagues show that immune imprinting impairs neutralizing antibody titers for bivalent mRNA vaccination against SARS-CoV-2 Omicron subvariants. Imprinting from three doses of monovalent vaccine can be alleviated by BA.5 or BQ-lineage breakthrough infection but not a booster.1Wang Q. Guo Y. Tam A.R. Valdez R. Gordon A. Liu L. Ho D.D. Deep immunological due to the ancestral spike in current COVID-19 vaccine.Cell Rep. Med. 2023; 4101258Google Scholar The concept "immune imprinting," also known as "original antigenic sin," is new; it originated 1960s with investigation responses divergent strains influenza viruses. Scientists found people had stronger toward they been exposed during childhood, while more antigenically distinct stimulated less effective responses.2Francis T. On Doctrine Original Antigenic Sin.Proc. Am. Phil. Soc. 1960; 104: 572-578Google Mechanistically, when different pathogen infect host cell, system dedicates most response recalling effectors used original exposure opposed generating new strains, thus resulting evasion. Immune induced either separately concomitantly one two mechanisms: favors recalled over de novo ("antigenic seniority"), other actively suppressed ("primary addiction"). Evidence both phenomena has severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination.3Evans J.P. S.-L. Challenges Prospects Developing Future Vaccines: Overcoming Sin Inducing Broadly Neutralizing Antibodies.J. Immunol. Crossref Scopus (0) Google seniority demonstrated fact upon vaccinated individuals variants such Alpha, Delta, Omicron, remains biased wild-type spike. Additionally, unvaccinated shown favorably induce antibodies cross-react common cold betacoronaviruses HKU1 OC43. Direct evidence primary addiction experiments tracked induction memory versus B cell boosting BA.1 spike, which resulted dramatic suppression favor spike.3Evans These findings emphasize strong influence on ability mount variable variants. Currently, biggest challenges faced pandemic maintenance efficacy continues evolve. end 2021 was marked emergence variant, characterized escape two-dose vaccines.4Schmidt F. Muecksch Weisblum Da Silva J. Bednarski E. Cho Z. Gaebler C. Caskey M. Nussenzweig M.C. et al.Plasma Neutralization Variant.N. Engl. 2022; 386: 599-601https://doi.org/10.1056/NEJMc2119641Crossref PubMed (261) Since then, virus evolved into numerous subvariants, including recent XBB Each these exhibited mounting escape,5He Wu Xu X. Xie Chai Zheng Zhou Qiao S. Huang al.An updated atlas evasion sub-variants BQ.1.1 XBB.Cell 4100991https://doi.org/10.1016/j.xcrm.2023.100991Abstract Full Text PDF (10) led decision reformulate measures. In September 2022, formulations Pfizer Moderna vaccines were made available. included BA.4/5 addition present help boost While inclusion helped nowhere near what wild-type/D614G all BA.4/5, still exhibiting reductions titers.6Cao Jian Yu Song W. Yisimayi An Chen Zhang N. al.Imprinted humoral immunity induces convergent RBD evolution.Nature. 614: 521-529https://doi.org/10.1038/s41586-022-05644-7Crossref (176) first indicators initial vaccine. there immune-evasive lineages BQ.1, BQ.1.1, BA.2.75, CH.1.1, well recombinant subvariants XBB.1.5, XBB.1.16, XBB.2.3, EG.5, FLip. this issue Cell Reports Medicine, al. sought corroborate idea demonstrating role BQ helping overcome imprinting.1Wang Breakthrough represents another means question, established stimulate infecting variant.7Evans Zeng Qu P. Faraone Y.-M. Carlin Bednash J.S. Lozanski G. Mallampalli al.Neutralization sub-lineages BA.1, BA.1.1, BA.2.Cell Host Microbe. 30: 1093-1102.e3https://doi.org/10.1016/j.chom.2022.04.014Abstract (74) data presented demonstrate critical course vaccines. They who booster containing little increase titer especially XBB.1.5 relative received lacking BA.4/5. contrast, at least experienced or, lesser extent, noticeable increases Using mapping analysis, discovered minimized distances between D614G, BA.5, BQ.1.1Wang method originally developed quantitatively measure differences based hemagglutination neutralization assay results.8Smith D.J. Lapedes A.S. Jong J.C. Bestebroer T.M. Rimmelzwaan G.F. Osterhaus A.D.M.E. Fouchier R.A.M. Mapping Genetic Evolution Influenza Virus.Science. 2004; 305: 371-376https://doi.org/10.1126/science.1097211Crossref (1276) More results studies have confirmed concern impaired EG.5.1 FLip.9Zhang Kempf Nehlmeier I. Cossmann Dopfer-Jablonka Stankov M.V. Schulz S.R. Jäck H.M. Behrens G.M.N. Pöhlmann Hoffmann Neutralisation sensitivity XBB.2.3.Lancet Infect. Dis. 23: e391-e392https://doi.org/10.1016/S1473-3099(23)00547-9Abstract (1) Scholar,10Faraone J.N. Goodarzi Saif L.J. Oltz E.M. K. Jones D. Gumina R.J. Evasion Membrane Fusion Subvariants XBB.2.3..Emerg Microbes 122270069Crossref Together, works are crucial informing strategies roll out fall 2023. Based others, become clear exclusion Omicron-lineage should caused earlier better protect circulation. Despite advances, surveillance characterization critical. chances XBBs will last we face, making timely important maintained control pandemic. authors declare no competing interests. vaccineWang al.Cell MedicineOctober 30, 2023In BriefWang report boosters did yield superior compared This result likely removed future Full-Text Open Access

Language: Английский

---

Enhanced potency of an IgM-like nanobody targeting conserved epitope in SARS-CoV-2 spike N-terminal domain

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 13, 2024

Abstract Almost all the neutralizing antibodies targeting receptor-binding domain (RBD) of spike (S) protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged emerging variants, such as Omicron and its sub-variants. This suggests that highly conserved epitopes are crucial for development antibodies. Here, we present one nanobody, N235, displaying broad neutralization SARS-CoV-2 prototype multiple including newly Cryo-electron microscopy demonstrates N235 binds a novel, conserved, cryptic epitope in N-terminal (NTD) S protein, which interferes with RBD neighboring protein. The mechanism interpreted via flow cytometry Western blot shows appears to induce S1 subunit shedding from trimeric complex. Furthermore, nano-IgM construct (MN235), engineered by fusing human IgM Fc region, displays prevention inducing cross-linking virus particles. Compared MN235 exhibits varied enhancement pseudotyped authentic viruses vitro. intranasal administration low doses can effectively prevent infection sub-variant BA.1 XBB vivo, suggesting it be developed promising prophylactic antibody cope ongoing future infection.

Language: Английский

---