IMPORTANCE Control of the global COVID-19 pandemic will require the development and deployment of safe and effective vaccines. OBJECTIVE To evaluate the immunogenicity of the Ad26.COV2.S vaccine (Janssen/Johnson & Johnson) in humans, including the kinetics, magnitude, and phenotype of SARS-CoV-2 spike-specific humoral and cellular immune responses. DESIGN, SETTING, AND PARTICIPANTS Twenty-five participants were enrolled from July 29, 2020, to August 7, 2020, and the follow-up for this day 71 interim analysis was completed on October 3, 2020; follow-up to assess durability will continue for 2 years. This study was conducted at a single clinical site in Boston, Massachusetts, as part of a randomized, double-blind, placebo-controlled phase 1 clinical trial of Ad26.COV2.S. INTERVENTIONS Participants were randomized to receive 1 or 2 intramuscular injections with 5 × 10 10 viral particles or 1 × 10 11 viral particles of Ad26.COV2.S vaccine or placebo administered on day 1 and day 57 (5 participants in each group). MAIN OUTCOMES AND MEASURES Humoral immune responses included binding and neutralizing antibody responses at multiple time points following immunization. Cellular immune responses included immunospot-based and intracellular cytokine staining assays to measure T-cell responses. RESULTS Twenty-five participants were randomized (median age, 42; age range, 22-52; 52% women, 44% male, 4% undifferentiated), and all completed the trial through the day 71 interim end point. Binding and neutralizing antibodies emerged rapidly by day 8 after initial immunization in 90% and 25% of vaccine recipients, respectively. By day 57, binding and neutralizing antibodies were detected in 100% of vaccine recipients after a single immunization. On day 71, the geometric mean titers of spike-specific binding antibodies were 2432 to 5729 and the geometric mean titers of neutralizing antibodies were 242 to 449 in the vaccinated groups. A variety of antibody subclasses, Fc receptor binding properties, and antiviral functions were induced. CD4+ and CD8+ T-cell responses were induced. CONCLUSION AND RELEVANCE In this phase 1 study, a single immunization with Ad26.COV2.S induced rapid binding and neutralization antibody responses as well as cellular immune responses. Two phase 3 clinical trials are currently underway to determine the efficacy of the Ad26.COV2.S vaccine.

27The SARS-CoV-2 pandemic has caused a severe international shortage of the nasopharyngeal 28 swabs that are required for collection of optimal specimens, creating a critical bottleneck 29 blocking clinical laboratories' ability to perform high-sensitivity virological testing for SARS-CoV-30 2. To address this crisis, we designed and executed an innovative, cooperative, rapid-response 31 translational-research program that brought together healthcare workers, manufacturers, and 32 scientists to emergently develop and clinically validate new swabs for immediate mass 33 production by 3D printing. We performed a multi-step preclinical evaluation on 160 swab 34 designs and 48 materials from 24 companies, laboratories, and individuals, and shared results 35 and other feedback via a public data repository (http://github.com/rarnaout/Covidswab/). We 36 validated four prototypes through an institutional review board (IRB)-approved clinical trial that 37 involved 276 outpatient volunteers who presented to our hospital's drive-through testing center 38 with symptoms suspicious for COVID-19. Each participant was swabbed with a reference swab 39 (the control) and a prototype, and SARS-CoV-2 reverse-transcriptase polymerase chain 40 reaction (RT-PCR) results were compared. All prototypes displayed excellent concordance with 41 the control (κ=0.85-0.89). Cycle-threshold (Ct) values were not significantly different between 42 each prototype and the control, supporting the new swabs' non-inferiority (Mann-Whitney U 43[MWU] p>0.05). Study staff preferred one of the prototypes over the others and the control swab 44 overall. The total time elapsed between identification of the problem and validation of the first 45 prototype was 22 days. Contact information for ordering can be found at http://printedswabs.org. 46Our experience holds lessons for the rapid development, validation, and deployment of new 47 technology for this pandemic and beyond. 48 on June 9, 2020 by guest

Rationale: Anaerobic bacteria are present in large numbers in the airways of people with cystic fibrosis (PWCF). In the gut, anaerobes produce short-chain fatty acids (SCFAs) that modulate immune and inflammatory processes.Objectives: To investigate the capacity of anaerobes to contribute to cystic fibrosis (CF) airway pathogenesis via SCFAs.Methods: Samples of 109 PWCF were processed using anaerobic microbiological culture with bacteria present identified by 16S RNA sequencing. SCFA levels in anaerobic supernatants and bronchoalveolar lavage (BAL) were determined by gas chromatography. The mRNA and/or protein expression of two SCFA receptors, GPR41 and GPR43, in CF and non-CF bronchial brushings and 16HBE14o 2 and CFBE41o 2 cells were evaluated using reverse transcription polymerase chain reaction, Western blot analysis, laser scanning cytometry, and confocal microscopy. SCFA-induced IL-8 secretion was monitored by ELISA.Measurements and Main Results: Fifty-seven (52.3%) of 109 PWCF were anaerobe positive. Prevalence increased with age, from 33.3% to 57.7% in PWCF younger (n = 24) and older (n = 85) than 6 years of age. All evaluated anaerobes produced millimolar concentrations of SCFAs, including acetic, propionic, and butyric acids. SCFA levels were higher in BAL samples of adults than in those of children. GPR41 levels were elevated in CFBE41o 2 versus 16HBE14o 2 cells; CF versus non-CF bronchial brushings; and 16HBE14o 2 cells after treatment with cystic fibrosis transmembrane conductance regulator inhibitor CFTR(inh)-172, CF BAL, or inducers of endoplasmic reticulum stress. SCFAs induced a dosedependent and pertussis toxin-sensitive IL-8 response in bronchial epithelial cells, with a higher production of IL-8 in CFBE41o 2 than in 16HBE14o 2 cells.Conclusions: This study illustrates that SCFAs contribute to excessive production of IL-8 in CF airways colonized with anaerobes via up-regulated GPR41.Keywords: anaerobic bacteria; cystic fibrosis; inflammation; short-chain fatty acids Correspondence and requests for reprints should be addressed to Bojana Mirković, Ph

Investigates managerial value systems and decision styles among expatriate and indigenous managers in the UAE. Provides support for the proposition that differences among expatriate and host country nationals are manifested in their value systems. Indicates that Arab expatriate and national managers display a high preference for participative and pseudo‐participative styles while foreign expatriates show a high commitment to consultative style. Finds work values to be significantly related to some decision styles.