Neutralising antibody escape of SARS‐CoV‐2 spike protein: Risk assessment for antibody‐based Covid‐19 therapeutics and vaccines

Reviews in Medical Virology, Год журнала: 2021, Номер 31(6)

Опубликована: Март 16, 2021

The Spike protein is the target of both antibody-based therapeutics (convalescent plasma, polyclonal serum, monoclonal antibodies) and vaccines. Mutations in could affect efficacy those treatments. Hence, monitoring mutations necessary to forecast readapt inventory therapeutics. Different phylogenetic nomenclatures have been used for currently circulating SARS-CoV-2 clades. has different hotspots mutation deletion, most dangerous immune escape being ones within receptor binding domain (RBD), such as K417N/T, N439K, L452R, Y453F, S477N, E484K, N501Y. Convergent evolution led combinations among In this review we focus on main variants concern, that is, so-called UK (B.1.1.7), South African (B.1.351) Brazilian (P.1) strains.

Язык: Английский

---

A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection

Cell Host & Microbe, Год журнала: 2021, Номер 29(5), С. 806 - 818.e6

Опубликована: Апрель 16, 2021

Язык: Английский

---

Analysis of Immune Escape Variants from Antibody-Based Therapeutics against COVID-19: A Systematic Review

International Journal of Molecular Sciences, Год журнала: 2021, Номер 23(1), С. 29 - 29

Опубликована: Дек. 21, 2021

The accelerated SARS-CoV-2 evolution under selective pressure by massive deployment of neutralizing antibody-based therapeutics is a concern with potentially severe implications for public health. We review here reports documented immune escape after treatment monoclonal antibodies and COVID-19-convalescent plasma (CCP). While the former mainly associated specific single amino acid mutations at residues within receptor-binding domain (e.g., E484K/Q, Q493R, S494P), few cases evasion CCP were recurrent deletions N-terminal spike protein ΔHV69-70, ΔLGVY141-144 ΔAL243-244). continuous genomic monitoring non-responders needed to better understand frequencies fitness emerging variants.

Язык: Английский

---

Predicting the zoonotic capacity of mammals to transmit SARS-CoV-2

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2021, Номер unknown

Опубликована: Фев. 19, 2021

Abstract Back and forth transmission of SARS-CoV-2 between humans animals may lead to wild reservoirs virus that can endanger efforts toward long-term control COVID-19 in people, protecting vulnerable animal populations are particularly susceptible lethal disease. Predicting high risk host species is key targeting field surveillance lab experiments validate zoonotic potential. A major bottleneck predicting hosts the small number with available molecular information about structure ACE2, a cellular receptor required for viral cell entry. We overcome this by combining species’ ecological biological traits 3D modeling protein interactions using machine learning methods. This approach enables predictions capacity over 5,000 mammals — an order magnitude more than previously possible. The accuracy achieved strongly corroborated vivo empirical studies. identify numerous common mammal whose predicted close proximity further enhance spillover spillback SARS-CoV-2. Our results reveal priority areas geographic overlap global hotspots potential new With sequence data only fraction species, predictive integrating across multiple scales offers conceptual advance expand our viruses similarly unknown potentially broad ranges.

Язык: Английский

---

Polyclonal hyper immunoglobulin: A proven treatment and prophylaxis platform for passive immunization to address existing and emerging diseases

Human Vaccines & Immunotherapeutics, Год журнала: 2021, Номер 18(2)

Опубликована: Май 19, 2021

Passive immunization with polyclonal hyper immunoglobulin (HIG) therapy represents a proven strategy by transferring immunoglobulins to patients confer immediate protection against range of pathogens including infectious agents and toxins. Distinct from active immunization, the is passive will clear system; therefore, administration an effective dose must be maintained for prophylaxis or treatment until natural adaptive immune response mounted pathogen/agent cleared. The current review provides overview this technology, key considerations address different pathogens, suggested improvements. reflect on learnings development HIGs in public health threats due Zika, influenza, severe acute respiratory syndrome coronavirus 2.

Язык: Английский

---

The Impact of Vaccination Frequency on COVID-19 Public Health Outcomes: A Model-Based Analysis

Vaccines, Год журнала: 2025, Номер 13(4), С. 368 - 368

Опубликована: Март 30, 2025

Background: While the rapid deployment of SARS-CoV-2 vaccines had a significant impact on ongoing COVID-19 pandemic, viral immune evasion and waning neutralizing antibody titers have degraded vaccine efficacy. Nevertheless, manufacturers public health authorities number options at their disposal to maximize benefits vaccination. In particular, effect booster schedules performance bears further study. Methods: To better understand performance, we used an agent-based modeling framework population pharmacokinetic model simulate boosting frequency durability protection against infection severe acute disease. Results: Our work suggests that repeated dosing frequent intervals (three or more times year) may offset degradation efficacy, preserving utility in managing pandemic. Conclusions: Given practical significance potential improvements utility, clinical research effects vaccination would be highly impactful. These findings are particularly relevant as worldwide reduced boosters once year less.

Язык: Английский

---

Beyond the new normal: Assessing the feasibility of vaccine-based suppression of SARS-CoV-2

PLoS ONE, Год журнала: 2021, Номер 16(7), С. e0254734 - e0254734

Опубликована: Июль 16, 2021

As the COVID-19 pandemic drags into its second year, there is hope on horizon, in form of SARS-CoV-2 vaccines which promise disease suppression and a return to pre-pandemic normalcy. In this study we critically examine basis for that hope, using an epidemiological modeling framework establish link between vaccine characteristics effectiveness bringing end unprecedented public health crisis. Our findings suggest social economic conditions without fully suppressing will lead extensive viral spread, resulting high burden even presence reduce risk infection mortality. points feasibility complete with population-level compliance are highly effective at reducing infection. Notably, vaccine-mediated reduction transmission critical suppression, order partially-effective play positive role complementary biomedical interventions measures must be deployed simultaneously.

Язык: Английский

---

Immunogenic amino acid motifs and linear epitopes of COVID-19 mRNA vaccines

PLoS ONE, Год журнала: 2021, Номер 16(9), С. e0252849 - e0252849

Опубликована: Сен. 9, 2021

Reverse vaccinology is an evolving approach for improving vaccine effectiveness and minimizing adverse responses by limiting immunizations to critical epitopes. Towards this goal, we sought identify immunogenic amino acid motifs linear epitopes of the SARS-CoV-2 spike protein that elicit IgG in COVID-19 mRNA recipients. Paired pre/post vaccination samples from N = 20 healthy adults, post-vaccine additional 13 individuals were used immunoprecipitate targets expressed a bacterial display random peptide library, preferentially recognized peptides mapped primary sequence. The data several distinct vaccine-induced IgG, subset those targeted natural infection, which may mimic 3-dimensional conformation (mimotopes). Dominant identified C-terminal domains S1 S2 subunits (aa 558-569, 627-638, 1148-1159) have been previously associated with neutralization vitro demonstrate identity bat coronavirus SARS-CoV, but limited homology non-pathogenic human coronavirus. should be considered context variants, immune escape therapy design moving forward.

Язык: Английский

---

ANALYSIS OF IMMUNE ESCAPE VARIANTS FROM ANTIBODY-BASED THERAPEUTICS AGAINST COVID-19

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2021, Номер unknown

Опубликована: Ноя. 11, 2021

Abstract Accelerated SARS-CoV-2 evolution under selective pressure by massive deployment of neutralizing antibody-based therapeutics is a concern with potentially severe implications for public health. We review here reports documented immune escape after treatment monoclonal antibodies and COVID19 convalescent plasma (CCP). While the former mainly associated specific single amino acid mutations at residues within receptor-binding domain (e.g., E484K/Q, Q493R, S494P), few cases evasion CCP were recurrent deletions N-terminal Spike protein (e.g, ΔHV69-70, ΔLGVY141-144 ΔAL243-244). Continuous genomic monitoring non-responders needed to better understand frequencies fitness emerging variants.

Язык: Английский

---

Beyond the new normal: assessing the feasibility of vaccine-based elimination of SARS-CoV-2

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2021, Номер unknown

Опубликована: Янв. 29, 2021

Abstract As the COVID-19 pandemic drags into its second year, there is hope on horizon, in form of SARS-CoV-2 vaccines which promise disease elimination and a return to pre-pandemic normalcy. In this study we critically examine basis for that hope, using an epidemiological modeling framework establish link between vaccine characteristics effectiveness bringing end unprecedented public health crisis. Our findings suggest do not prevent infection will allow extensive endemic spread upon social economic conditions. Vaccines only reduce symptomatic or mortality fail mitigate serious risks, particularly over-65 population, likely resulting hundreds thousands US deaths yearly basis. points possibility complete with high population-level compliance highly effective at reducing infection. Notably, vaccine-mediated reduction transmission critical elimination, order partially-effective play positive role other stackable (complementary) interventions must be deployed simultaneously.

Язык: Английский

---