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J Am Med Dir Assoc ; 2021 Dec 22.
Article in English | MEDLINE | ID: covidwho-1587373
Nat Protoc ; 16(6): 3114-3140, 2021 06.
Article in English | MEDLINE | ID: covidwho-1203437


Virus neutralization assays measure neutralizing antibodies in serum and plasma, and the plaque reduction neutralization test (PRNT) is considered the gold standard for measuring levels of these antibodies for many viral diseases. We have developed procedures for the standard PRNT, microneutralization assay (MNA) and pseudotyped virus neutralization assay (PNA) for severe acute respiratory syndrome coronavirus 2. The MNA offers advantages over the PRNT by reducing assay time, allowing increased throughput and reducing operator workload while remaining dependent upon the use of wild-type virus. This ensures that all severe acute respiratory syndrome coronavirus 2 antigens are present, but Biosafety Level 3 facilities are required. In addition to the advantages of MNA, PNA can be performed with lower biocontainment (Biosafety Level 2 facilities) and allows for further increases in throughput. For each new vaccine, it is critical to ensure good correlation of the neutralizing activity measured using PNA against the PRNT or MNA. These assays have been used in the development and licensure of the ChAdOx1 nCoV-19 (AstraZeneca; Oxford University) and Ad26.COV2.S (Janssen) coronavirus disease 2019 vaccines and are critical for demonstrating bioequivalence of future vaccines.

Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Neutralization Tests/methods , SARS-CoV-2/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/blood , COVID-19/prevention & control , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Humans , Neutralization Tests/economics , Time Factors
Cell ; 184(8): 2201-2211.e7, 2021 04 15.
Article in English | MEDLINE | ID: covidwho-1086820


SARS-CoV-2 has caused over 2 million deaths in little over a year. Vaccines are being deployed at scale, aiming to generate responses against the virus spike. The scale of the pandemic and error-prone virus replication is leading to the appearance of mutant viruses and potentially escape from antibody responses. Variant B.1.1.7, now dominant in the UK, with increased transmission, harbors 9 amino acid changes in the spike, including N501Y in the ACE2 interacting surface. We examine the ability of B.1.1.7 to evade antibody responses elicited by natural SARS-CoV-2 infection or vaccination. We map the impact of N501Y by structure/function analysis of a large panel of well-characterized monoclonal antibodies. B.1.1.7 is harder to neutralize than parental virus, compromising neutralization by some members of a major class of public antibodies through light-chain contacts with residue 501. However, widespread escape from monoclonal antibodies or antibody responses generated by natural infection or vaccination was not observed.

Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , CHO Cells , COVID-19/epidemiology , Chlorocebus aethiops , Cricetulus , HEK293 Cells , Humans , Pandemics , Protein Binding , Structure-Activity Relationship , Vero Cells
Front Public Health ; 8: 590275, 2020.
Article in English | MEDLINE | ID: covidwho-983747


The COVID-19 pandemic has laid bare the inadequacy of the U.S. healthcare system to deliver timely and resilient care. According to the American Hospital Association, the pandemic has created a $202 billion loss across the healthcare industry, forcing health care systems to lay off workers and making hospitals scramble to minimize supply chain costs. However, as the demand for personal protective equipment (PPE) grows, hospitals have sacrificed sustainable solutions for disposable options that, although convenient, will exacerbate supply strains, financial burden, and waste. We advocate for reusable gowns as a means to lower health care costs, address climate change, and improve resilience while preserving the safety of health care workers. Reusable gowns' polyester material provides comparable capacity to reduce microbial cross-transmission and liquid penetration. In addition, previous hospitals have reported a 50% cost reduction in gown expenditures after adopting reusable gowns; given the current 2000% price increase in isolation gowns during COVID-19, reusable gown use will build both healthcare resilience and security from price fluctuations. Finally, with the United States' medical waste stream worsening, reusable isolation gowns show promising reductions in energy and water use, solid waste, and carbon footprint. The gowns are shown to withstand laundering 75-100 times in contrast to the single-use disposable gown. The circumstances of the pandemic forewarn the need to shift our single-use PPE practices to standardized reusable applications. Ultimately, sustainable forms of protective equipment can help us prepare for future crises that challenge the resilience of the healthcare system.

COVID-19/prevention & control , Disposable Equipment/economics , Equipment Reuse/economics , Health Personnel/statistics & numerical data , Infection Control/economics , Pandemics/prevention & control , Protective Clothing/economics , Adult , Disposable Equipment/statistics & numerical data , Equipment Reuse/statistics & numerical data , Female , Humans , Infection Control/statistics & numerical data , Male , Middle Aged , Occupational Exposure/economics , Occupational Exposure/statistics & numerical data , Pandemics/statistics & numerical data , Protective Clothing/statistics & numerical data , United States