Antibody evasion by SARS-CoV-2 Omicron subvariants BA.2.12.1, BA.4 and BA.5

Nature, Год журнала: 2022, Номер 608(7923), С. 603 - 608

Опубликована: Июль 5, 2022

Abstract SARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 have surged notably to become dominant in the United States South Africa, respectively 1,2 . These new carrying further mutations their spike proteins raise concerns that they may evade neutralizing antibodies, thereby compromising efficacy of COVID-19 vaccines therapeutic monoclonals. We now report findings from a systematic antigenic analysis these surging subvariants. is only modestly (1.8-fold) more resistant sera vaccinated boosted individuals than BA.2. However, substantially (4.2-fold) thus likely lead vaccine breakthrough infections. Mutation at residue L452 found both facilitates escape some antibodies directed so-called class 2 3 regions receptor-binding domain The F486V mutation certain 1 but compromises affinity for viral receptor. R493Q reversion mutation, however, restores receptor consequently fitness BA.4/5. Among authorized clinical use, bebtelovimab retains full potency against lineage continues evolve, successively yielding are not transmissible also evasive antibodies.

Язык: Английский

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Origin, virological features, immune evasion and intervention of SARS-CoV-2 Omicron sublineages

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Июль 19, 2022

Recently, a large number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continuously emerged and posed major threat to global public health. Among them, particularly, Omicron variant (B.1.1.529), first identified in November 2021, carried numerous mutations its spike protein (S), then quickly spread around the world. Currently, has expanded into more than one hundred sublineages, such as BA.1, BA.2, BA.2.12.1, BA.4 BA.5, which have already become globally dominant variants. Different from other concern (VOCs) SARS-CoV-2, sublineages exhibit increased transmissibility immune escape neutralizing antibodies generated through previous infection or vaccination, caused re-infections breakthrough infections. In this prospective, we focused on origin, virological features, evasion intervention will benefit development next-generation vaccines therapeutics, including pan-sarbecovirus universal anti-CoV combat currently circulating future emerging well SARS-CoV-2

Язык: Английский

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Fast and sensitive CRISPR detection by minimized interference of target amplification

Nature Chemical Biology, Год журнала: 2024, Номер 20(7), С. 885 - 893

Опубликована: Фев. 8, 2024

Язык: Английский

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Conversion of monoclonal IgG to dimeric and secretory IgA restores neutralizing ability and prevents infection of Omicron lineages

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(3)

Опубликована: Янв. 9, 2024

The emergence of Omicron lineages and descendent subvariants continues to present a severe threat the effectiveness vaccines therapeutic antibodies. We have previously suggested that an insufficient mucosal immunoglobulin A (IgA) response induced by mRNA is associated with surge in breakthrough infections. Here, we further show intramuscular and/or inactivated cannot sufficiently boost secretory IgA uninfected individuals, particularly against variant. thus engineered characterized recombinant monomeric, dimeric, IgA1 antibodies derived from four neutralizing IgG monoclonal (mAbs 01A05, rmAb23, DXP-604, XG014) targeting receptor-binding domain spike protein. Compared their parental antibodies, dimeric showed higher activity different variants concern (VOCs), part due increased avidity. Importantly, or form DXP-604 antibody significantly outperformed its antibody, neutralized BA.1, BA.2, BA.4/5 25- 75-fold increase potency. In human angiotensin converting enzyme 2 (ACE2) transgenic mice, single intranasal dose conferred prophylactic protection BA.5. Thus, delivered nasal administration may potentially be exploited for treatment prevention infection, thereby providing alternative tool combating immune evasion current circulating and, potentially, future VOCs.

Язык: Английский

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Tuberculosis vaccines and therapeutic drug: challenges and future directions

Molecular Biomedicine, Год журнала: 2025, Номер 6(1)

Опубликована: Янв. 22, 2025

Abstract Tuberculosis (TB) remains a prominent global health challenge, with the World Health Organization documenting over 1 million annual fatalities. Despite deployment of Bacille Calmette-Guérin (BCG) vaccine and available therapeutic agents, escalation drug-resistant Mycobacterium tuberculosis strains underscores pressing need for more efficacious vaccines treatments. This review meticulously maps out contemporary landscape TB development, focus on antigen identification, clinical trial progress, obstacles future trajectories in research. We spotlight innovative approaches, such as multi-antigen mRNA technology platforms. Furthermore, delves into current therapeutics, particularly multidrug-resistant (MDR-TB), exploring promising agents like bedaquiline (BDQ) delamanid (DLM), well potential host-directed therapies. The hurdles development encompass overcoming diversity, enhancing effectiveness across diverse populations, advancing novel Future initiatives emphasize combinatorial strategies, anti-TB compounds targeting pathways, personalized medicine treatment prevention. notable advances, persistent challenges diagnostic failures protracted regimens continue to impede progress. work aims steer research endeavors toward groundbreaking providing crucial insights prevention strategies.

Язык: Английский

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The lethal K18-hACE2 knock-in mouse model mimicking the severe pneumonia of COVID-19 is practicable for antiviral development

Emerging Microbes & Infections, Год журнала: 2024, Номер 13(1)

Опубликована: Май 16, 2024

Animal models of COVID-19 facilitate the development vaccines and antivirals against SARS-CoV-2. The efficacy or may differ in different animal with varied degrees disease. Here, we introduce a mouse model expressing human angiotensin-converting enzyme 2 (ACE2). In this model,

Язык: Английский

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Antibody evasion by SARS-CoV-2 Omicron subvariants BA.2.12.1, BA.4, and BA.5

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Май 26, 2022

Abstract SARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 have surged dramatically to become dominant in the United States South Africa, respectively 1,2 . These novel carrying additional mutations their spike proteins raise concerns that they may further evade neutralizing antibodies, thereby compromising efficacy of COVID-19 vaccines therapeutic monoclonals. We now report findings from a systematic antigenic analysis these surging subvariants. is only modestly (1.8-fold) more resistant sera vaccinated boosted individuals than BA.2. However, substantially (4.2-fold) thus likely lead vaccine breakthrough infections. Mutation at residue L452 found both facilitates escape some antibodies directed so-called class 2 3 regions receptor-binding domain The F486V mutation certain 1 but compromises affinity for viral receptor. R493Q reversion mutation, however, restores receptor consequently fitness BA.4/5. Among authorized clinical use, bebtelovimab retains full potency against lineage continues evolve, successively yielding are not transmissible also evasive antibodies.

Язык: Английский

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Comparative Review of the State of the Art in Research on the Porcine Epidemic Diarrhea Virus and SARS-CoV-2, Scope of Knowledge between Coronaviruses

Viruses, Год журнала: 2024, Номер 16(2), С. 238 - 238

Опубликована: Фев. 2, 2024

This review presents comparative information corresponding to the progress in knowledge of some aspects infection by porcine epidemic diarrhea virus (PEDV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronaviruses. PEDV is an alphacoronavirus great economic importance due million-dollar losses it generates pig industry. has many similarities SARS-CoV-2 betacoronavirus that causes COVID-19 disease. possible scenarios for based on collected literature tools or strategies currently developed would be useful research. The speed study generation control pandemic was derived from infections caused other human coronaviruses such as (SARS) middle east (MERS). Therefore, obtained several coronaviruses, current future behavior could inferred and, with large amount COVID-19, improved probably new emerging re-emerging

Язык: Английский

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A broad neutralizing nanobody against SARS-CoV-2 engineered from an approved drug

Cell Death and Disease, Год журнала: 2024, Номер 15(6)

Опубликована: Июнь 28, 2024

Abstract SARS-CoV-2 infection is initiated by Spike glycoprotein binding to the human angiotensin-converting enzyme 2 (ACE2) receptor via its domain. Blocking this interaction has been proven be an effective approach inhibit virus infection. Here we report discovery of a neutralizing nanobody named VHH60, which was directly produced from engineering library based on commercialized within very short period. VHH60 competes with ACE2 bind domain protein at S 351 , 470-471 and 493-494 as determined structural analysis, affinity 2.56 nM. It inhibits infections both ancestral strain pseudotyped viruses harboring wildtype, key mutations or variants nanomolar level. Furthermore, suppressed propagation 50-fold better protected mice death for twice long control group after nasal in vivo. Therefore, not only powerful promising profile disease but also provides evidence highly rapid generating therapeutic nanobodies.

Язык: Английский

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ACE2-using merbecoviruses: Further evidence of convergent evolution of ACE2 recognition by NeoCoV and other MERS-CoV related viruses

Cell Insight, Год журнала: 2024, Номер 3(1), С. 100145 - 100145

Опубликована: Янв. 30, 2024

Angiotensin-converting enzyme 2 (ACE2) was recognized as an entry receptor shared by coronaviruses from

Язык: Английский

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