Analysis of Immune Escape Variants from Antibody-Based Therapeutics against COVID-19: A Systematic Review.
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ABSTRACT:
SUBMITTER: Focosi D
PROVIDER: S-EPMC8744556 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Monoclonal antibodies (mAbs) with neutralizing activity against SARS-CoV-2 have demonstrated clinical benefit in cases of mild to moderate SARS-CoV-2 infection, substantially reducing the risk for hospitalization and severe disease1-4. Treatment generally requires the administration of high doses of these mAbs with limited efficacy in preventing disease complications or mortality among hospitalized COVID-19 patients5. Here we report the development and evaluation of Fc-optimized anti-SARS-CoV-2 mAbs with superior potency to prevent or treat COVID-19 disease. In several animal models of COVID-19 disease6,7, we demonstrate that selective engagement of activating FcγRs results in improved efficacy in both preventing and treating disease-induced weight loss and mortality, significantly reducing the dose required to confer full protection upon SARS-CoV-2 challenge and treatment of pre-infected animals. Our results highlight the importance of FcγR pathways in driving antibody-mediated antiviral immunity, while excluding any pathogenic or disease-enhancing effects of FcγR engagement of anti-SARS-CoV-2 antibodies upon infection. These findings have important implications for the development of Fc-engineered mAbs with optimal Fc effector function and improved clinical efficacy against COVID-19 disease.
| S-EPMC8168397 | biostudies-literature
Project description: Not available
| S-EPMC9638196 | biostudies-literature
Project description:The emergence of SARS-CoV-2 and subsequent COVID-19 pandemic has resulted in a significant global public health burden, leading to an urgent need for effective therapeutic strategies. In this article, we review the role of SARS-CoV-2 neutralizing antibodies (nAbs) in the clinical management of COVID-19 and provide an overview of recent randomized controlled trial data evaluating nAbs in the ambulatory, hospitalized and prophylaxis settings. Two nAb cocktails (casirivimab/imdevimab and bamlanivimab/etesevimab) and one nAb monotherapy (bamlanivimab) have been granted Emergency Use Authorization by the US Food and Drug Administration for the treatment of ambulatory patients who have a high risk of progressing to severe disease, and the European Medicines Agency has similarly recommended both cocktails and bamlanivimab monotherapy for use in COVID-19 patients who do not require supplemental oxygen and who are at high risk of progressing to severe COVID-19. Efficacy of nAbs in hospitalized patients with COVID-19 has been varied, potentially highlighting the challenges of antiviral treatment in patients who have already progressed to severe disease. However, early data suggest a promising prophylactic role for nAbs in providing effective COVID-19 protection. We also review the risk of treatment-emergent antiviral resistant "escape" mutants and strategies to minimize their occurrence, discuss the susceptibility of newly emerging SARS-COV-2 variants to nAbs, as well as explore administration challenges and ways to improve patient access.
| S-EPMC8067572 | biostudies-literature
Project description:BackgroundWith the emergence and spread of new SARS-CoV-2 variants, concerns are raised about the effectiveness of the existing vaccines to protect against these new variants. Although many vaccines were found to be highly effective against the reference COVID-19 strain, the same level of protection may not be found against mutation strains. The objective of this study is to systematically review relevant studies in the literature and compare the efficacy of COVID-19 vaccines against new variants.MethodsWe conducted a systematic review of research published in Scopus, PubMed, and Google Scholar until 30 August 2021. Studies including clinical trials, prospective cohorts, retrospective cohorts, and test negative case-controls that reported vaccine effectiveness against any COVID-19 variants were considered. PRISMA recommendations were adopted for screening, eligibility, and inclusion.Results129 unique studies were reviewed by the search criteria, of which 35 met the inclusion criteria. These comprised of 13 test negative case-control studies, 6 Phase 1-3 clinical trials, and 16 observational studies. The study location, type, vaccines used, variants considered, and reported efficacies were highlighted.ConclusionFull vaccination (two doses) offers strong protection against Alpha (B.1.1.7) with 13 out of 15 studies reporting more than 84% efficacy. The results are not conclusive against the Beta (B.1.351) variant for fully vaccinated individuals with 4 out of 7 studies reporting efficacies between 22 and 60% and 3 out of 7 studies reporting efficacies between 75 and 100%. Protection against Gamma (P.1) variant was lower than 50% according to two studies in fully vaccinated individuals. The data on Delta (B.1.617.2) variant is limited but indicates lower protection compared to other variants.
| S-EPMC8622454 | biostudies-literature
Project description:Facing the COVID-19 global healthcare crisis, scientists worldwide are collaborating to develop prophylactic and therapeutic interventions against the disease. Antibody therapeutics hold enormous promise for the treatment of COVID-19. In March 2020, the Chinese Antibody Society, in collaboration with The Antibody Society, initiated the "COVID-19 Antibody Therapeutics Tracker" ("Tracker") (https://chineseantibody.org/covid-19-track/) program to track the antibody-based COVID-19 interventions in preclinical and clinical development globally. The data are collected from the public domain and verified by volunteers on an ongoing basis. Here, we present exploratory data analyses and visualization to demonstrate the latest trends of COVID-19 antibody development, based on data for over 150 research and development programs and molecules included in the "Tracker" as of 8 August 2020. We categorized the data mainly by their targets, formats, development status, developers and country of origin. Although details are limited in some cases, all of the anti-SARS-CoV-2 antibody candidates appear to target the viral spike protein (S protein), and most are full-length monoclonal antibodies. Most of the current COVID-19 antibody therapeutic candidates in clinical trials are repurposed drugs aimed at targets other than virus-specific proteins, while most of these virus-specific therapeutic antibodies are in discovery or preclinical studies. As of 8 August 2020, eight antibody candidates targeting the SARS-CoV-2 S protein have entered clinical studies, including LY-CoV555, REGN-COV2, JS016, TY027, CT-P59, BRII-196, BRII-198 and SCTA01. Ongoing clinical trials of SARS-CoV-2 neutralizing antibodies will help define the utility of these antibodies as a new class of therapeutics for treating COVID-19 and future coronavirus infections.
| S-EPMC7454247 | biostudies-literature
Project description:This project is aimed at characterizing the interactions of SARS-CoV-2 Spike protein and its variants with multiple full-length antibodies and monitoring the accompanying conformational dynamics. Different categories of antibodies are tested that recognize different domains of the Spike protein. The project aims at identifying the effects of weak, moderate and strong neutralizing antibodies on Spike protein and decipher their mechanisms of action. In addition to the direct binding effects, distal allosteric effects are also determined. A range of biophysical experiments, biochemical assays, and molecular dynamics simulations are used as orthogonal approaches. The rationale is to identify regions on the SARS-CoV-2 Spike protein that acts as indicators for antibody binding and use these hotspots to develop better neutralizing antibodies against SARS-CoV-2 and any future viral pandemics.
2023-10-09 | PXD043818 | Pride
Project description:As SARS-CoV-2 has been circulating for over a year, dozens of vaccine candidates are under development or in clinical use. The BNT162b2 mRNA COVID-19 vaccine induces spike protein-specific neutralizing antibodies associated with protective immunity. The emergence of the B.1.1.7 and B.1.351 variants has raised concerns of reduced vaccine efficacy and increased re-infection rates. Here we show, that after the second dose, the sera of BNT162b2-vaccinated health care workers (n = 180) effectively neutralize the SARS-CoV-2 variant with the D614G substitution and the B.1.1.7 variant, whereas the neutralization of the B.1.351 variant is five-fold reduced. Despite the reduction, 92% of the seronegative vaccinees have a neutralization titre of >20 for the B.1.351 variant indicating some protection. The vaccinees' neutralization titres exceeded those of recovered non-hospitalized COVID-19 patients. Our work provides evidence that the second dose of the BNT162b2 vaccine induces cross-neutralization of at least some of the circulating SARS-CoV-2 variants.
| S-EPMC8239026 | biostudies-literature
Project description:We propose a new hypothesis that explains the maintenance and evolution of MHC polymorphism. It is based on two phenomena: the constitution of the repertoire of naive T lymphocytes and the evolution of the pathogen and its impact on the immune memory of T lymphocytes. Concerning the latter, pathogen evolution will have a different impact on reinfection depending on the MHC allomorph. If a mutation occurs in a given region, in the case of MHC allotypes, which do not recognize the peptide in this region, the mutation will have no impact on the memory repertoire. In the case where the MHC allomorph binds to the ancestral peptides and not to the mutated peptide, that individual will have a higher chance of being reinfected. This difference in fitness will lead to a variation of the allele frequency in the next generation. Data from the SARS-CoV-2 pandemic already support a significant part of this hypothesis and following up on these data may enable it to be confirmed. This hypothesis could explain why some individuals after vaccination respond less well than others to variants and leads to predict the probability of reinfection after a first infection depending upon the variant and the HLA allomorph.
| S-EPMC8910380 | biostudies-literature
Project description:IntroductionAfter the results of phase III vaccine studies became available, the leading oncology societies recommended two doses of COVID-19 vaccination to all patients with cancer with no specific recommendation for tumor type and active treatments. However, the data on the COVID-19 vaccine efficacy in cancer patients is limited due to exclusion of cancer patients from most vaccine clinical trials. Therefore, we systemically reviewed the available evidence evaluating the antibody responses in cancer patients.MethodsWe conducted a systematic search from the Pubmed database and calculated risk differences (RD) and 95% confidence intervals (CI) to compare seroconversion rates between cancer patients and controls using the Review Manager software, version 5.3.ResultsOur systematic search retrieved a total 27 studies and we included 17 studies with control arms in the analyses. Cancer patients had significantly lower seroconversion rates (37.3%) than controls (74.1%) (RD: -0.44, 95% CI: -0.52, -0.35, p<0.001) with first vaccine dose. After two doses, the seroconversion rates were 99.6% in control arm and 78.3% in cancer patients (RD: -0.19, 95% CI: -0.28, -0.10, p<0.001). The difference in seroconversion rates was more pronounced patients with hematologic malignancies (72.6%) (RD: -0.25, 95% CI: -0.27, -0.22, p<0.001) than patients with solid tumors (91.6%) (RD: -0.09, 95% CI: -0.13, -0.04, p<0.003) and patients in remission (RD: -0.10, 95% CI: -0.14, -0.06, p<0.001).ConclusionIn conclusion, COVID-19 vaccine seroconversion rates were significantly lower in patients with hematological malignancies and patients under active treatment. Further research focusing on the approaches to improve vaccine efficacy and exploration of novel treatment options is urgently needed for these patients.
| S-EPMC8599356 | biostudies-literature
Project description:Understanding the systems biology approaches for promoting the development of new therapeutic drugs is attaining importance nowadays. The threat of COVID-19 outbreak needs to be vanished for global welfare, and every section of research is focusing on it. There is an opportunity for finding new, quick, and accurate tools for developing treatment options, including the vaccine against COVID-19. The review at this moment covers various aspects of pathogenesis and host factors for exploring the virus target and developing suitable therapeutic solutions through systems biology tools. Furthermore, this review also covers the extensive details of multiomics tools i.e., transcriptomics, proteomics, genomics, lipidomics, immunomics, and in silico computational modeling aiming towards the study of host-virus interactions in search of therapeutic targets against the COVID-19.
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