Immunity elicited by natural infection or Ad26.COV2.S vaccination protects hamsters against SARS-CoV-2 variants of concern.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern have emerged and may pose a threat to both the efficacy of vaccines based on the original WA1/2020 strain and the natural immunity induced by infection with earlier SARS-CoV-2 variants. We investigated how mutations in the spike protein of circulating SARS-CoV-2 variants, which have been shown to partially evade neutralizing antibodies, affect natural and vaccine-induced immunity. We adapted a Syrian hamster model of moderate to severe clinical disease for two variant strains of SARS-CoV-2: B.1.1.7 (alpha variant) and B.1.351 (beta variant). We then assessed the protective efficacy conferred by either natural immunity from WA1/2020 infection or by vaccination with a single dose of the adenovirus serotype 26 vaccine, Ad26.COV2.S. Primary infection with the WA1/2020 strain provided potent protection against weight loss and viral replication in lungs after rechallenge with WA1/2020, B.1.1.7, or B.1.351. Ad26.COV2.S induced cross-reactive binding and neutralizing antibodies that were reduced against the B.1.351 strain compared with WA1/2020 but nevertheless still provided robust protection against B.1.351 challenge, as measured by weight loss and pathology scoring in the lungs. Together, these data support hamsters as a preclinical model to study protection against emerging variants of SARS-CoV-2 conferred by prior infection or vaccination.

Manufacturing biological medicines on demand: Safety and efficacy of granulocyte colony-stimulating factor in a mouse model of total body irradiation.

Protein therapeutics, also known as biologics, are currently manufactured at centralized facilities according to rigorous protocols. The manufacturing process takes months and the delivery of the biological products needs a cold chain. This makes it less responsive to rapid changes in demand. Here, we report on technology application for on-demand biologics manufacturing (Bio-MOD) that can produce safe and effective biologics from cell-free systems at the point of care without the current challenges of long-term storage and cold-chain delivery. The objective of the current study is to establish proof-of-concept safety and efficacy of Bio-MOD-manufactured granulocyte colony-stimulating factor (G-CSF) in a mouse model of total body irradiation at a dose estimated to induce 30% lethality within the first 30 days postexposure. To illustrate on-demand Bio-MOD production feasibility, histidine-tagged G-CSF was manufactured daily under good manufacturing practice-like conditions prior to administration over a 16-day period. Bio-MOD-manufactured G-CSF improved 30-day survival when compared with saline alone (p = .073). In addition to accelerating recovery from neutropenia, the platelet and hemoglobin nadirs were significantly higher in G-CSF-treated animals compared with saline-treated animals (p < .05). The results of this study demonstrate the feasibility of consistently manufacturing safe and effective on-demand biologics suitable for real-time release.