作者: Hanley, Patrick W. ; Machado, Viviane ; Patel, Ami ; Frase, Drew ; Francica, Joseph R. ; Chokkalingam, Neethu ; Feldmann, Heinz ; Griffin, Amanda J. ; Choi, Jihae ; Feldmann, Friederike ; Parzych, Elizabeth M. ; Generotti, Allison ; Gary, Ebony N. ; Bharti, Suman ; Schouest, Blake ; Lovaglio, Jamie ; Smith, Trevor R. F. ; Esser, Mark T. ; Nguyen, Brian ; Smith, Brian J. ; Rosenke, Kyle ; Rosenthal, Kim ; Ali, Ali R. ; Lewis, Matt ; Kulkarni, Abhijeet ; Walker, Susanne N. ; Shaia, Carl ; Weiner, David B. ; Kulp, Daniel W.

COVID-19 remains a major public health concern. Monoclonal antibodies have received emergency use authorization (EUA) for pre-exposure prophylaxis against COVID-19 among high-risk groups for treatment of mild to moderate COVID-19. In addition to recombinant biologics, engineered synthetic DNA-encoded antibodies (DMAb) are an important strategy for direct in vivo delivery of protective mAb. A DMAb cocktail was synthetically engineered to encode the immunoglobulin heavy and light chains of two different two different Fc-engineered anti-SARS-CoV-2 antibodies. The DMAbs were designed to enhance in vivo expression and delivered intramuscularly to cynomolgus and rhesus macaques with a modified in vivo delivery regimen. Serum levels were detected in macaques, along with specific binding to SARS-CoV-2 spike receptor binding domain protein and neutralization of multiple SARS-CoV-2 variants of concern in pseudovirus and authentic live virus assays. Prophylactic administration was protective in rhesus macaques against signs of SARS-CoV-2 (USA-WA1/2020) associated disease in the lungs. Overall, the data support further study of DNA-encoded antibodies as an additional delivery mode for prevention of COVID-19 severe disease. These data have implications for human translation of gene-encoded mAbs for emerging infectious diseases and low dose mAb delivery against COVID-19.

2024-11-01·Talanta

Single-particle rotational sensing for analyzing the neutralization activity of antiviral antibodies

Article

作者: Li, Huiwen ; Shang, Jinhui ; Xiong, Bin ; Huan, Shuangyan ; Liu, Xixuan ; Sun, Shijie

Due to the pathogen-specific targeting, neutralization capabilities, and enduring efficacy, neutralizing antibodies (NAs) have received widespread attentions as a critical immunotherapeutic strategy against infectious viruses. However, because of the high variability and complexity of pathogens, rapid determination of neutralization activity of antiviral antibodies remains a challenge. Here, we report a new method, named as out-of-plane polarization imaging based single-particle rotational sensing, for rapid analysis of neutralization activity of antiviral antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using the spike protein functionalized gold nanorods (AuNRs) and angiotensin-converting enzyme 2 (ACE2) coated gold nanoparticles (AuNPs) as the rotational sensors and chaperone probes, we demonstrated the single-particle rotational sensing strategy for the measurement of rotational diffusion coefficient of the chaperone-bound rotational sensors caused by the specific spike protein-ACE2 interactions. This enables us to measure the neutralizing activity of neutralizing antibody from the analysis of dose-dependent changes in rotational diffusion coefficient (Dr) of the rotational sensors upon the treatment of SARS-CoV-2 antibody. With this technique, we achieved the quantitative determination of neutralization activity of a commercially available SARS-CoV-2 antibody (IC50, 294.1 ng/mL) with satisfying accuracy and anti-interference ability. This simple and robust method holds the potential for rapid and accurate evaluation of neutralization activity against different pathogenic viruses.

2024-10-01·Lupus

Anti-SARS-CoV-2 mRNA vaccination among patients living with SLE in Sweden: Coverage and clinical effectiveness

Article

作者: Arkema, Elizabeth V ; Mageau, Arthur ; Svenungsson, Elisabet ; Simard, Julia F

Objectives To describe the uptake of anti-SARS-CoV2 vaccination in 2021 and investigate vaccine effectiveness in systemic lupus erythematosus (SLE) patients in Sweden. Methods The cumulative incidence of first anti-SARS-CoV2 vaccination was estimated among SLE patients from the Swedish National Patient Register and matched comparators living in Sweden on January 1, 2021. To assess vaccine effectiveness, we included the individuals who received two doses of anti-SARS-CoV2 mRNA vaccines before year 2022, with no COVID-19 diagnosis code before the 2nd vaccine dose. Hospitalization rates with COVID-19 as main diagnosis during the year after second dose were compared between SLE patients and comparators in multivariable-adjusted marginal Cox models, overall and stratified by immunosuppressive treatment received during the year before second vaccine dose. Results Vaccination uptake was similar between SLE patients and comparators. By December 2021, 9% of both SLE and comparators had not received any vaccine doses. Among 5585 SLE patients and 37,102 comparators, 11 COVID-19 hospitalizations in the SLE group and 20 in the comparators occurred. SLE was associated with a higher risk of COVID-19 hospitalization (HR = 3.47, 95%CI 1.63-7.39). The HR was higher for immunosuppressive-treated SLE (7.03 95%CI 3.00-16.46) than for immunosuppressive-untreated (1.50 95%CI 0.34-6.60). Vaccination of immunosuppressive-untreated SLE patients had similar effectiveness as comparators. Conclusion Anti-SARS-CoV2 vaccination coverage was similar between SLE patients and the general population in Sweden. Even though the incidence of post-vaccination COVID-19 hospitalization was very low, vaccine effectiveness was diminished in SLE patients compared to the general population and lowest in those treated with immunosuppressants.

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