Review of therapeutic mechanisms and applications based on SARS-CoV-2 neutralizing antibodies

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: March 16, 2023

COVID-19 pandemic is a global public health emergency. Despite extensive research, there are still few effective treatment options available today. Neutralizing-antibody-based treatments offer broad range of applications, including the prevention and acute infectious diseases. Hundreds SARS-CoV-2 neutralizing antibody studies currently underway around world, with some already in clinical applications. The development opens up new therapeutic option for COVID-19. We intend to review our current knowledge about antibodies targeting various regions (i.e., RBD regions, non-RBD host cell targets, cross-neutralizing antibodies), as well scientific evidence neutralizing-antibody-based based on convalescent plasma therapy, intravenous immunoglobulin, monoclonal antibodies, recombinant drugs. functional evaluation vitro or vivo assays) also discussed. Finally, issues field therapies highlighted.

Language: Английский

---

Pharmacokinetic interaction assessment of an HIV broadly neutralizing monoclonal antibody VRC07-523LS: a cross-protocol analysis of three phase 1 trials in people without HIV

BMC Immunology, Journal Year: 2025, Volume and Issue: 26(1)

Published: Feb. 19, 2025

Language: Английский

---

Development of antiviral drugs for COVID-19 in 2025: unmet needs and future challenges

Expert Review of Anti-infective Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

The success in the COVID-19 pandemic containment largely originated from vaccine- and infection-elicited immunity, with SARS-CoV-2 infection only marginally mitigated by availability of antiviral drugs. current lack effective prophylactic therapeutic agents immunocompromised patients highlights need for a radical change design both drug manufacturing clinical trials. In this review authors summarize their suggestions manufacturers, reviewing classes small molecule antivirals passive immunotherapies highlighting limitations unexploited potential. Molecular serological testing can improve appropriateness. Efficacy be improved combining different while preserving economical sustainability. Respiratory delivery should better investigated

Language: Английский

---

Tixagevimab + cilgavimab against SARS-CoV-2: the preclinical and clinical development and real-world evidence

Expert Opinion on Drug Discovery, Journal Year: 2023, Volume and Issue: 18(3), P. 231 - 245

Published: Jan. 17, 2023

Direct-acting SARS-CoV-2 antiviral monoclonal antibodies have been an integral part of therapeutic strategies against COVID-19 pandemic. The strategy was jeopardized by the emergence new variants and resistant strains, making many quickly obsolete. Nevertheless, a possible consists in use antibody cocktails development cilgavimab + tixagevimab combination is placed this context.In review, we describe cocktail, from pre-clinical to real-world evidence.The clinical followed similar path that developed earlier stages Both convalescent plasma shown be effective trials prophylaxis early therapy. This cocktail has found its position therapy especially immunocompromised subjects for whom vaccine prevention not feasible. strategy, together with more stable pandemic situation, could ensure certain longevity drug resistance, when compared other antibodies. Recently emerged Omicron sub-lineages demonstrated ability escape cocktail's activity so future treatment compromised.

Language: Английский

---

Allogeneic hematopoietic stem cell transplantation in the COVID-19 era

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 22, 2023

Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) recipients are especially vulnerable to coronavirus disease 19 (COVID-19), because of their profound immunodeficiency. Indeed, the first pandemic wave was marked by a high mortality rate in this population. Factors increasing immunodepression such as older age, immunosuppressive treatments or short delay between transplant and infection appear worsen prognosis. Many changes clinical practice had be implemented order limit risk, including postponing for non-malignant diseases, preference local rather than international donations peripheral blood stem cell source, widespread use cryopreservation. The great revolution COVID-19 came from development mRNA vaccines that have shown able prevent severe forms disease. More 75% allo-HSCT develop seroconversion after 2 doses vaccine. Multiple studies identified lymphopenia, exposure anti-CD20 therapies, post-transplant period factors associated with poor response vaccination. repeated injections vaccine, third dose, not only improves but also intensifies immune response, both B cells T cells. Vaccines an effective well-tolerated method high-risk Some investigated possibility protection being transferred vaccinated donor recipient, encouraging initial results. However, dynamic mutations escape virus can lead breakthrough infections new variants individuals still represent threat recipients. New challenges include need adapt vaccine emerging variants.

Language: Английский

---

SARS-CoV-2 Evolution: Implications for Diagnosis, Treatment, Vaccine Effectiveness and Development

Vaccines, Journal Year: 2024, Volume and Issue: 13(1), P. 17 - 17

Published: Dec. 28, 2024

The COVID-19 pandemic, driven by the rapid evolution of SARS-CoV-2 virus, presents ongoing challenges to global public health. is characterized rapidly evolving mutations, especially in (but not limited to) spike protein, complicating predictions about its evolutionary trajectory. These mutations have significantly affected transmissibility, immune evasion, and vaccine efficacy, leading multiple pandemic waves with over half a billion cases seven million deaths globally. Despite several strategies, from development administration design availability antivirals, including monoclonal antibodies, already having been employed, persistent circulation virus emergence new variants continue result high case numbers fatalities. In past four years, immense research efforts contributed much our understanding viral pathogenesis mechanism, syndrome, host-microbe interactions, effective vaccines, diagnostic tools, treatments. focus this review provide comprehensive analysis functional impact on diagnosis, treatments, effectiveness. We further discuss safety pregnancy implications hybrid immunity long-term protection against infection, as well latest developments pan-coronavirus nasal formulations, emphasizing need for continued surveillance, research, adaptive health strategies response race.

Language: Английский

---

Respiratory delivery of passive immunotherapies for SARS-CoV-2 prophylaxis and therapy

Human Vaccines & Immunotherapeutics, Journal Year: 2023, Volume and Issue: 19(2)

Published: Aug. 1, 2023

Convalescent plasma has been extensively tested during the COVID-19 pandemic as a transfusion product. Similarly, monoclonal antibodies have largely administered either intravenously or intramuscularly. Nevertheless, when used against respiratory pathogen, delivery is preferable to maximize amount of antibody that reaches entry door in order prevent sustained viral multiplication. In this narrative review, we review different types inhalation device and summarize evidence from animal models early clinical trials supporting (for prophylactic therapeutic purposes) convalescent (either full antibodies, single-chain variable fragments, camelid-derived heavy-chain only antibodies). Preliminary evidences suggest similar safety noninferior efficacy, but efficacy evaluation still limited.

Language: Английский

---

A Review of Hematological Complications and Treatment in COVID-19

Hematology Reports, Journal Year: 2023, Volume and Issue: 15(4), P. 562 - 577

Published: Oct. 13, 2023

COVID-19, caused by SARS-CoV-2, and its variants have spread rapidly across the globe in past few years, resulting millions of deaths worldwide. Hematological diseases complications associated with COVID-19 severely impact mortality morbidity rates patients; therefore, there is a need for oversight on what pharmaceutical therapies are prescribed to hematologically at-risk patients. Thrombocytopenia, hemoglobinemia, leukopenia, leukocytosis all seen at increased patients infected become more prominent severe COVID-19. Further, therapeutics may be hematological complications, this became important immunocompromised conditions as they higher risk after treatment. Thus, it understand treat underlying caution. changes during infection treatment because serve biomarkers well evaluate response, which will help changing strategies. In literature review, we discuss mechanisms, groups, adverse effects commonly used therapies, followed events that could arise due therapeutic agents

Language: Английский

---

Vaccine Based on Recombinant Fusion Protein Combining Hepatitis B Virus PreS with SARS-CoV-2 Wild-Type- and Omicron-Derived Receptor Binding Domain Strongly Induces Omicron-Neutralizing Antibodies in a Murine Model

Vaccines, Journal Year: 2024, Volume and Issue: 12(3), P. 229 - 229

Published: Feb. 23, 2024

Background: COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a recurrent endemic disease affecting whole world. Since November 2021, Omicron and its subvariants have dominated in spread of disease. In order to prevent courses disease, vaccines are needed boost maintain antibody levels capable neutralizing Omicron. Recently, we produced characterized SARS-CoV-2 vaccine based on recombinant fusion protein consisting hepatitis B virus (HBV)-derived PreS two wild-type RBDs. Objectives: To develop PreS-RBD which induces high Omicron-specific antibodies. Methods: We designed, produced, compared strain-specific (wild-type: W-PreS-W; Omicron: O-PreS-O), bivalent (mix W-PreS-W O-PreS-O) chimeric (i.e., W-PreS-O) subunit vaccines. Immunogens were vitro using chemical methods, mass spectrometry, circular dichroism combination with thermal denaturation immunological methods. addition, BALB/c mice immunized aluminum–hydroxide-adsorbed proteins aluminum hydroxide alone placebo) study specific cytokine responses, safety neutralization. Results: Defined pure immunogens could be significant quantities as secreted folded mammalian cells. The antibodies induced after vaccination different doses strain-specific, reacted RBD dose-dependent manner resulted mixed Th1/Th2 immune response. Interestingly, RBD-specific IgG comparable, but W-PreS-O-induced neutralization titers against (median VNT50: 5000) seven- twofold higher than W-PreS-W- O-PreS-O-specific ones, respectively, they six-fold those vaccine. Conclusion: Among tested immunogens, vaccine, W-PreS-O, highest Thus, W-PreS-O seems highly promising COVID-19 candidate for further preclinical clinical evaluation.

Language: Английский

---

Efficacy and safety of tixagevimab/cilgavimab as passive immunisation against COVID-19 infections in patients with hematological malignancies

Annals of Hematology, Journal Year: 2024, Volume and Issue: 103(6), P. 2123 - 2131

Published: March 2, 2024

Language: Английский

---