Evolving Real-World Effectiveness of Monoclonal Antibodies for Treatment of COVID-19

Annals of Internal Medicine, Journal Year: 2023, Volume and Issue: 176(4), P. 496 - 504

Published: April 1, 2023

Background: Treatment guidelines and U.S. Food Drug Administration emergency use authorizations (EUAs) of monoclonal antibodies (mAbs) for treatment high-risk outpatients with mild to moderate COVID-19 changed frequently as different SARS-CoV-2 variants emerged. Objective: To evaluate whether early outpatient mAbs, overall by mAb product, presumed variant, immunocompromised status, is associated reduced risk hospitalization or death at 28 days. Design: Hypothetical pragmatic randomized trial from observational data comparing mAb-treated patients a propensity score–matched, nontreated control group. Setting: Large health care system. Participants: High-risk eligible under any EUA positive test result 8 December 2020 31 August 2022. Intervention: Single-dose intravenous bamlanivimab, bamlanivimab–etesevimab, sotrovimab, bebtelovimab, subcutaneous casirivimab–imdevimab administered within 2 days result. Measurements: The primary outcome was among treated versus group (no ≥3 after date). Results: 4.6% in 2571 7.6% 5135 (risk ratio [RR], 0.61 [95% CI, 0.50 0.74]). In sensitivity analyses, the corresponding RRs 1- 3-day grace periods were 0.59 0.49, respectively. subgroup those receiving mAbs when Alpha Delta be predominant had estimated 0.55 0.53, respectively, compared 0.71 Omicron variant period. Relative estimates individual products all suggested lower death. Among patients, RR 0.45 (CI, 0.28 0.71). Limitations: Observational study design, date rather than genotyping, no on symptom severity, partial vaccination status. Conclusion: Early various variants. Primary Funding Source: None.

Language: Английский

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Peptidomimetics as potent dual SARS-CoV-2 cathepsin-L and main protease inhibitors: In silico design, synthesis and pharmacological characterization

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 266, P. 116128 - 116128

Published: Jan. 9, 2024

In this paper we present the design, synthesis, and biological evaluation of a new series peptidomimetics acting as potent anti-SARS-CoV-2 agents. Starting from our previously described Main Protease (M

Language: Английский

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SARS-CoV-2 Specific Nanobodies Neutralize Different Variants of Concern and Reduce Virus Load in the Brain of h-ACE2 Transgenic Mice

Viruses, Journal Year: 2024, Volume and Issue: 16(2), P. 185 - 185

Published: Jan. 25, 2024

Since the beginning of COVID-19 pandemic, there has been a significant need to develop antivirals and vaccines combat disease. In this work, we developed llama-derived nanobodies (Nbs) directed against receptor binding domain (RBD) other domains Spike (S) protein SARS-CoV-2. Most Nbs with neutralizing properties were RBD able block S-2P/ACE2 interaction. Three recognized N-terminal (NTD) S-2P protein. Intranasal administration induced protection ranging from 40% 80% after challenge WA1/2020 strain in k18-hACE2 transgenic mice. Interestingly, was associated reduction virus replication nasal turbinates load brain. Employing pseudovirus neutralization assays, identified capacity Alpha, Beta, Delta, Omicron variants, including Nb capable all variants tested. Furthermore, cocktails different performed better than individual at two (B.1.529 BA.2). Altogether, data suggest potential SARS-CoV-2 specific for intranasal treatment encephalitis.

Language: Английский

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From Detection to Protection: Antibodies and Their Crucial Role in Diagnosing and Combatting SARS-CoV-2

Vaccines, Journal Year: 2024, Volume and Issue: 12(5), P. 459 - 459

Published: April 25, 2024

Understanding the antibody response to SARS-CoV-2, virus responsible for COVID-19, is crucial comprehending disease progression and significance of vaccine therapeutic development. The emergence highly contagious variants poses a significant challenge humoral immunity, underscoring necessity grasping intricacies specific antibodies. This review emphasizes pivotal role antibodies in shaping immune responses their implications diagnosing, preventing, treating SARS-CoV-2 infection. It delves into kinetics characteristics explores current antibody-based diagnostics, discussing strengths, clinical utility, limitations. Furthermore, we underscore potential SARS-CoV-2-specific antibodies, various therapies such as monoclonal polyclonal anti-cytokines, convalescent plasma, hyperimmunoglobulin-based therapies. Moreover, offer insights vaccines, emphasizing neutralizing order confer immunity along with emerging concern (VOCs) circulating Omicron subvariants. We also highlight challenges field, risks antibody-dependent enhancement (ADE) shed light on associated original antigenic sin (OAS) effect long COVID. Overall, this intends provide valuable insights, which are advancing sensitive diagnostic tools, identifying efficient therapeutics, developing effective vaccines combat evolving threat global scale.

Language: Английский

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Nanobodies: from high-throughput identification to therapeutic development

Molecular & Cellular Proteomics, Journal Year: 2024, Volume and Issue: unknown, P. 100865 - 100865

Published: Oct. 1, 2024

Language: Английский

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Immunogenicity and Pre-Clinical Efficacy of an OMV-Based SARS-CoV-2 Vaccine

Vaccines, Journal Year: 2023, Volume and Issue: 11(10), P. 1546 - 1546

Published: Sept. 29, 2023

The vaccination campaign against SARS-CoV-2 relies on the world-wide availability of effective vaccines, with a potential need 20 billion vaccine doses to fully vaccinate world population. To reach this goal, manufacturing and logistic processes should be affordable all countries, irrespective economical climatic conditions. Outer membrane vesicles (OMVs) are bacterial-derived that can engineered incorporate heterologous antigens. Given inherent adjuvanticity, such modified OMVs used as vaccines induce potent immune responses associated proteins. Here, we show peptides derived from receptor binding motif (RBM) spike protein elicit an response in vaccinated mice, resulting production neutralizing antibodies (nAbs) titre higher than 1:300. immunity induced by is sufficient protect animals intranasal challenge SARS-CoV-2, preventing both virus replication lungs pathology infection. Furthermore, effectively decorated RBM Omicron BA.1 variant nAbs BA.5, measured using pseudovirus neutralization infectivity assay. Importantly, RBM438–509 ancestral-OMVs elicited which efficiently neutralize vitro homologous ancestral strain, BA.5 variants ranging 1:100 1:1500, suggesting its use targeting diverse variants. Altogether, given convenience ease engineering, distribution, our results demonstrate OMV-based crucial addition currently available.

Language: Английский

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Effectiveness of vaccination against SARS-CoV-2 and the need for alternative preventative approaches in immunocompromised individuals: a narrative review of systematic reviews

Expert Review of Vaccines, Journal Year: 2023, Volume and Issue: 22(1), P. 341 - 365

Published: March 15, 2023

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including administration of booster doses, continues to be the most effective method for controlling COVID-19-related complications progression illness and death. However, there is mounting evidence that more needs done protect individuals with compromised immune function.Here, we review effectiveness COVID-19 vaccination in immunocompromised patients, those primary immunodeficiencies, HIV, cancer (including hematological malignancies), solid organ transplant recipients, chronic kidney disease, as reported systematic reviews/meta-analyses published over a 12-month period PubMed. Given varied responses patients function, major goal this analysis was try identify specific risk-factors related vaccine failure.COVID-19 remains global problem, new variants concern emerging at regular intervals. There an ongoing need optimal strategies combat pandemic. In addition, alternative treatment approaches are needed who may not mount adequate response current vaccines. Identification high-risk introduction newer antiviral such monoclonal antibodies will offer physicians therapeutic options vulnerable individuals.

Language: Английский

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Immunogenicity and pre-clinical efficacy of an OMV-based SARS-CoV-2 vaccine

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

Published: May 25, 2023

The vaccination campaign against SARS-CoV-2 relies on the world-wide availability of effective vaccines, with a potential need 20 billion vaccine doses to fully vaccinate world population. To reach this goal, manufacturing and logistic processes should be affordable all countries, irrespectively economical climatic conditions. Outer membrane vesicles (OMV) are bacterial-derived that can engineered incorporate heterologous antigens. Given inherent adjuvanticity, such modified OMV used as induce potent immune responses associated protein. Here we show OMVs peptides derived from receptor binding motif (RBM) spike protein elicit an response in vaccinated mice, resulting production neutralizing antibodies (nAbs). immunity induced by is sufficient protect animals intranasal challenge SARS-CoV-2, preventing both virus replication lungs pathology infection. Furthermore, effectively decorated RBM Omicron BA.1 variant nAbs BA.5, judged pseudovirus infectivity assay. Importantly,

Language: Английский

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Immunoliposomes As a Promising Antiviral Agent against SARS-CoV-2

Doklady Biochemistry and Biophysics, Journal Year: 2024, Volume and Issue: 514(1), P. 6 - 10

Published: Jan. 7, 2024

Abstract According to the World Health Organization, as of January 3, 2020 September 13, 2023, there were approximately 23 million confirmed cases COVID-19 reported in Russian Federation, about 400 thousand which fatal. Considering high rate mutation RNA-containing virus genome, inevitably leads emergence new infectious strains (Eris and Pyrola), search for medicinal antiviral agents remains an urgent task. Moreover, taking into account actively mutating receptor-binding domain, this task requires fundamentally solutions. This study proposes a candidate immunoliposomal drug that targets S protein SARS-CoV-2 by monoclonal neutralizing antibody P4A1 ensures penetration highly active ribonuclease virus-infected cell, degrades, among cellular RNA, viral RNA too. We demonstrate more than 40-fold increase activity developed compared free antibody.

Language: Английский

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Analysis of how antigen mutations disrupt antibody binding interactions toward enabling rapid and reliable antibody repurposing

mAbs, Journal Year: 2024, Volume and Issue: 17(1)

Published: Dec. 17, 2024

Antibody repurposing is the process of changing a known antibody so that it binds to mutated antigen. One findings emerge from Coronavirus Disease 2019 (COVID-19) pandemic was possible repurpose neutralizing antibodies for Severe Acute Respiratory Syndrome, related disease, work COVID-19. Thus, pathway prepare and respond future pandemics, as well personalizing cancer therapies. For be successfully repurposed, necessary know both how antigen mutations disrupt their binding they should recover binding, with this describing an analysis address first these topics. Every point mutation in interface 246 antibody–protein complexes were analyzed using Rosetta molecular mechanics force field. The results highlight number features affect including effects mutating critical hotspot residues versus other positions, many are likely prevalence indirect on relative importance attractive repulsive energies. These data expected useful guiding experiments.

Language: Английский

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