A structure-function analysis shows SARS-CoV-2 BA.2.86 balances antibody escape and ACE2 affinity

Cell Reports Medicine, Год журнала: 2024, Номер 5(5), С. 101553 - 101553

Опубликована: Май 1, 2024

BA.2.86, a recently described sublineage of SARS-CoV-2 Omicron, contains many mutations in the spike gene. It appears to have originated from BA.2 and is distinct XBB variants responsible for infections 2023. The global spread plethora BA.2.86 has caused concern that it may possess greater immune-evasive potential, leading new wave infection. Here, we examine ability evade antibody response infection using panel vaccinated or naturally infected sera find shows marginally less immune evasion than XBB.1.5. We locate antigenic landscape recent look at its escape panels potent monoclonal antibodies generated against contemporary infections. demonstrate, provide structural explanation for, increased affinity ACE2, which increase transmissibility.

Язык: Английский

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Clearance of persistent SARS-CoV-2 associates with increased neutralizing antibodies in advanced HIV disease post-ART initiation

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 15, 2024

Abstract SARS-CoV-2 clearance requires adaptive immunity but the contribution of neutralizing antibodies and T cells in different immune states is unclear. Here we ask which responses associate with long-term infection HIV-mediated immunosuppression after suppressive antiretroviral therapy (ART) initiation. We assembled a cohort infected people South Africa ( n = 994) including participants advanced HIV disease characterized by due to cell depletion. Fifty-four percent had prolonged (>1 month). In five vaccinated tested, associates emergence not specific CD8 cells, while CD4 were determined low numbers. Further, complete suppression required for clearance, although it necessary an effective vaccine response. Persistent led evolution, virus extensive neutralization escape Delta variant participant. The results provide evidence that are recovery, ART curtail evolution co-infecting pathogens reduce individual health consequences as well public risk linked generation mutants.

Язык: Английский

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SARS-CoV-2 resistance to monoclonal antibodies and small-molecule drugs

Cell chemical biology, Год журнала: 2024, Номер 31(4), С. 632 - 657

Опубликована: Апрель 1, 2024

Over four years have passed since the beginning of COVID-19 pandemic. The scientific response has been rapid and effective, with many therapeutic monoclonal antibodies small molecules developed for clinical use. However, given ability viruses to become resistant antivirals, it is perhaps no surprise that field identified resistance nearly all these compounds. Here, we provide a comprehensive review profile each therapeutics. We hope this resource provides an atlas mutations be aware agent, particularly as springboard considerations next generation antivirals. Finally, discuss outlook thoughts moving forward in how continue manage this, next,

Язык: Английский

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Characterisation of the antibody-mediated selective pressure driving intra-host evolution of SARS-CoV-2 in prolonged infection

PLoS Pathogens, Год журнала: 2024, Номер 20(10), С. e1012624 - e1012624

Опубликована: Окт. 15, 2024

Neutralising antibodies against the SARS-CoV-2 spike (S) protein are major determinants of protective immunity, though insufficient antibody responses may cause emergence escape mutants. We studied humoral immune response causing intra-host evolution in a B-cell depleted, haemato-oncologic patient experiencing clinically severe, prolonged infection with virus lineage B.1.177.81. Following bamlanivimab treatment at an early stage infection, developed bamlanivimab-resistant mutation, S:S494P. After five weeks apparent genetic stability, additional substitutions and deletions within N-terminal domain (NTD) receptor binding (RBD) S was observed. Notably, composition frequency mutations changed short period unprecedented dynamic. The triple mutant S:Delta141-4 E484K S494P became dominant until elimination. Routine serology revealed no evidence patient. A detailed analysis variant-specific by pseudotyped neutralisation test, surrogate immunoglobulin-capture enzyme immunoassay showed that onset IgM-dominated coincided appearance mutations. formation neutralising correlated One year later, experienced mild re-infection Omicron BA.1.18, which treated sotrovimab resulted increase Omicron-reactive antibodies. In conclusion, endogenous immunocompromised NTD RBD virus. Although elimination ultimately achieved, this escaped detection routine diagnosis created situation temporarily favouring rapid various mutants known epidemiological relevance.

Язык: Английский

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The consequences of SARS-CoV-2 within-host persistence

Nature Reviews Microbiology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 25, 2024

Язык: Английский

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