Nucleocapsid-specific antibody function is associated with therapeutic benefits from COVID-19 convalescent plasma therapy.

Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP), a passive polyclonal antibody therapeutic agent, has had mixed clinical results. Although antibody neutralization is the predominant approach to benchmarking CCP efficacy, CCP may also influence the evolution of the endogenous antibody response. Using systems serology to comprehensively profile severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) functional antibodies of hospitalized people with COVID-19 enrolled in a randomized controlled trial of CCP (ClinicalTrials.gov: NCT04397757), we find that the clinical benefits of CCP are associated with a shift toward reduced inflammatory Spike (S) responses and enhanced nucleocapsid (N) humoral responses. We find that CCP has the greatest clinical benefit in participants with low pre-existing anti-SARS-CoV-2 antibody function and that CCP-induced immunomodulatory Fc glycan profiles and N immunodominant profiles persist for at least 2 months. We highlight a potential mechanism of action of CCP associated with durable immunomodulation, outline optimal patient characteristics for CCP treatment, and provide guidance for development of a different class of COVID-19 hyperinflammation-targeting antibody therapeutic agents.

Feasibility of hepatitis C virus testing and linkage in community supervision offices: Great potential but persistent challenges.

BACKGROUND: Persons involved with the justice system have an elevated risk of hepatitis C virus (HCV) yet remain marginalized from treatment. Efforts to eliminate HCV will require targeted interventions within the justice system effective at providing diagnosis and treatment. METHODS: We implemented a novel HCV screening and treatment intervention for persons under community supervision in Rhode Island, USA during April 2018--March 2020. Participants received rapid point-of-care HCV antibody testing onsite and referral to community laboratory and treatment services as indicated. We assessed the HCV care cascade to identify areas for improvement. RESULTS: Overall, 483 individuals were screened for HCV antibody; 85 (18%) were positive. A minority of participants with positive HCV antibody tests (n=25/85, 29%) presented to community laboratories for confirmatory testing. Among participants that received HCV viral load results and linked to a treatment provider (n=12), four initiated treatment, three had record of completing treatment, and two were confirmed to have achieved cure. CONCLUSION: Linkage to HCV viral load testing and treatment was challenging in this community supervision population, with substantial loss to follow-up at each step of the HCV cascade. Community supervision remains an important venue for case identification but substantial barriers to accessing HCV treatment exist. Innovative HCV diagnosis and treatment strategies are needed for community supervision populations.

Mining HIV controllers for broad and functional antibodies to recognize and eliminate HIV-infected cells.

HIV monoclonal antibodies for viral reservoir eradication strategies will likely need to recognize reactivated infected cells and potently drive Fc-mediated innate effector cell activity. We systematically characterize a library of 185 HIV-envelope-specific antibodies derived from 15 spontaneous HIV controllers (HCs) that selectively exhibit robust serum Fc functionality and compared them to broadly neutralizing antibodies (bNAbs) in clinical development. Within the 10 antibodies with the broadest cell-recognition capability, seven originated from HCs and three were bNAbs. V3-loop-targeting antibodies are enriched among the top cell binders, suggesting the V3-loop may be selectively exposed and accessible on the cell surface. Fc functionality is more variable across antibodies, which is likely influenced by distinct binding topology and corresponding Fc accessibility, highlighting not only the importance of target-cell recognition but also the need to optimize for Fc-mediated elimination. Ultimately, our results demonstrate that this comprehensive selection process can identify monoclonal antibodies poised to eliminate infected cells.