Search

Background: AZD2816 is a variant-adapted COVID-19 vaccine that expresses the full-length SARS-CoV-2 beta variant spike protein but is otherwise similar to AZD1222 (ChAdOx1 nCoV-19). This study aimed to evaluate the safety and immunogenicity of AZD1222 or AZD2816 (or both) primary-series vaccination in a cohort of adult participants who were previously unvaccinated., Methods: In this phase 2/3, randomised, multinational, active-controlled, non-inferiority, immunobridging study, adult participants previously unvaccinated for COVID-19 were enrolled at 16 study sites in Brazil, South Africa, Poland, and the UK. Participants were stratified by age, sex, and comorbidity and randomly assigned 5:5:5:2 to receive a primary series of AZD1222 (AZD1222 group), AZD2816 (AZD2816 [4-week] group), or AZD1222-AZD2816 (AZD1222-AZD2816 group) at 4-week dosing intervals, or AZD2816 at a 12-week interval (AZD2816 [12-week] group) and evaluated for safety and immunogenicity through 180 days after dose 2. Primary outcomes were safety (rates of solicited adverse events occurring during 7 days and unsolicited adverse events occurring during 28 days after each dose) and immunogenicity (non-inferiority of pseudovirus neutralising antibody geometric mean titre [GMT], GMT ratio margin of 0·67, and seroresponse rate, rate difference margin of -10%, recorded 28 days after dose 2 with AZD2816 [4-week interval] against beta vs AZD1222 against ancestral SARS-CoV-2) in participants who were seronegative at baseline. This trial is registered with ClinicalTrials.gov, NCT04973449, and is completed., Findings: Between July 7 and Nov 12, 2021, 1449 participants were assigned to the AZD1222 group (n=413), the AZD2816 (4-week) group (n=415), the AZD1222-AZD2816 group (n=412), and the AZD2816 (12-week) group (n=209). Ten (2·6%) of 378 participants who were seronegative at baseline in the AZD1222 group, nine (2·4%) of 379 in the AZD2816 (4-week) group, eight (2·1%) of 380 in the AZD1222-AZD2816 group, and 11 (5·8%) of 191 in the AZD2816 (12-week) group had vaccine-related unsolicited adverse events. Serious adverse events were recorded in one (0·3%) participant in the AZD1222 group, one (0·3%) in the AZD2816 (4-week) group, two (0·5%) in the AZD1222-AZD2816 group, and none in the AZD2816 (12-week) group. Co-primary immunogenicity endpoints were met: neutralising antibody GMT (ratio 1·19 [95% CI 1·08-1·32]; lower bound greater than 0·67) and seroresponse rate (difference 1·7% [-3·1 to 6·5]; lower bound greater than -10%) at 28 days after dose 2 were non-inferior in the AZD2816 (4-week) group against beta versus in the AZD1222 group against ancestral SARS-CoV-2. Seroresponse rates were highest with AZD2816 against beta (12-week interval 94·3% [95% CI 89·4-97·3]; 4-week interval 85·7% [81·5-89·2]) and with AZD1222 (84·6% [80·3-88·2]) against ancestral SARS-CoV-2., Interpretation: Primary series of AZD1222 and AZD2816 were well tolerated, with no emergent safety concerns. Both vaccines elicited robust immunogenicity against beta and ancestral SARS-CoV-2 with greater responses demonstrated when testing against SARS-CoV-2 strains that matched those targeted by the respective vaccine. These findings demonstrate the continued importance of ancestral COVID-19 vaccines in protecting against severe COVID-19 and highlight the feasibility of using the ChAdOx1 platform to develop COVID-19 vaccines against future SARS-CoV-2 variants., Funding: AstraZeneca., Competing Interests: Declaration of interests SACC declares participation in the clinical development, with University of Oxford, of the vaccines described in this Article, membership on CureVac and Clover advisory boards, and institutional research grants from AstraZeneca. BJ is an employee of Cytel and is currently on assignment to AstraZeneca. QEB declares institutional funding, the provision of study materials, or both from the Wits Health Consortium, the Bill & Melinda Gates Foundation, the South African Medical Research Council, and AstraZeneca, as well as research grants or contracts from Regeneron, Novo Nordisk, Avillion, GlaxoSmithKline, Novavax, Sinovac, Johnson & Johnson, and Pfizer pharmaceuticals. PKA declares institutional grants to support the conduct of the study from AstraZeneca and the UK Vaccine Taskforce via the UK National Institute for Health Research (NIHR). HB is an employee of Bogier consulting and is currently on assignment to AstraZeneca. EJK is an employee of Sanofi. SM is an employee of Exploristics and is currently on assignment to AstraZeneca. EPM declares no competing interests. TL declares consulting fees from Vaccitech on an unrelated project, an honorarium from Seqirus on an unrelated project, an institutional grant from the UK Vaccine Taskforce via the NIHR, work-related investments, and is a named inventor on a patent application for a vaccine against SARS-CoV-2. JJL declares no competing interests. MNR declares institutional support for the study from AstraZeneca. AJP is Chair of the UK Department of Health and Social Care’s Joint Committee on Vaccination and Immunisation (JCVI) but does not participate in the JCVI COVID-19 committee. AJP also declares membership of the WHO’s Strategic Advisory Group of Experts on Immunization until January, 2022; provision of advice to Shionogi on COVID-19; and funding from the NIHR, AstraZeneca, the Bill & Melinda Gates Foundation, Wellcome, the UK Research and Innovation Medical Research Council, the Serum Institute of India, and the Coalition for Epidemic Preparedness Innovations. University of Oxford has entered a partnership with AstraZeneca for the development of COVID-19 vaccines; TL, MNR, SB, PKA, and AJP are contributors to the intellectual property licensed by Oxford University Innovation to AstraZeneca. AA, TA, EJK, MK, UO, SS, KS, AS, TV, and JAG are, or were, employees of and may hold (or have held) stock or stock options in AstraZeneca. MSMdOP declares no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Children with COVID-associated multisystem inflammatory syndrome (MIS-C) may develop severe disease. We explored the association of admission echocardiographic and laboratory parameters with MIS-C disease severity. This retrospective, single center study of consecutive MIS-C patients (4/2020-12/2021) excluded those with preexisting cardiomyopathy, congenital heart disease, or prior cardiotoxic therapy. Our hypothesis was that worse admission echocardiographic and laboratory parameters were associated with more severe disease based on vasoactive medication use. Univariable and multivariable logistic regression models assessed the association between vasoactive medication use and baseline variables. Of 118 MIS-C patients, median age was 7.8 years (IQR 4.6, 11.8), 48% received vasoactive medication. Higher admission brain natriuretic peptide [OR 1.07 (95% CI 1.02,1.14), p = 0.019], C-reactive protein [OR 1.08 (1.03,1.14), p = 0.002], troponin [OR 1.05 (1.02,1.1), p = 0.015]; lower left ventricular ejection fraction [LVEF, OR 0.96 (0.92,1), p = 0.042], and worse left atrial reservoir strain [OR 0.96 (0.92,1), p = 0.04] were associated with vasoactive medication use. Only higher CRP [OR 1.07 (1.01, 1.11), p = 0.034] and lower LVEF [0.91 (0.84,0.98), p = 0.015] remained independently significant. Among those with normal admission LVEF (78%, 92/118), 43% received vasoactive medication and only higher BNP [OR 1.09 (1.02,1.19), p = 0.021 per 100 pg/mL] and higher CRP [OR 1.07 (1.02,1.14), p = 0.013] were associated with use of vasoactive medication. Nearly half of all children admitted for MIS-C subsequently received vasoactive medication, including those admitted with a normal LVEF. Similarly, admission strain parameters were not discriminatory. Laboratory markers of systemic inflammation and cardiac injury may better predict early MIS-C disease severity., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: This study aimed to evaluate AZD2816, a variant-updated COVID-19 vaccine expressing the full-length SARS-CoV-2 beta (B.1.351) variant spike protein that is otherwise similar to AZD1222 (ChAdOx1 nCoV-19), and AZD1222 as third-dose boosters., Methods: This phase 2/3, partly double-blinded, randomised, active-controlled study was done at 19 sites in the UK and four in Poland. Adult participants who had received a two-dose AZD1222 or mRNA vaccine primary series were randomly assigned by means of an Interactive Response Technology-Randomisation and Trial Supply Management system (1:1 within each primary-series cohort, stratified by age, sex, and comorbidities) to receive AZD1222 or AZD2816 (intramuscular injection; 5 × 10 10 viral particles). Participants, investigators, and all sponsor staff members involved in study conduct were masked to randomisation. AZD1222 and AZD2816 doses were prepared by unmasked study staff members. The primary objectives were to evaluate safety and humoral immunogenicity (non-inferiority of day-29 pseudovirus neutralising antibody geometric mean titre [GMT] against ancestral SARS-CoV-2: AZD1222 booster vs AZD1222 primary series [historical controls]; margin 0·67; SARS-CoV-2-seronegative participants). This study is registered with ClinicalTrials.gov, NCT04973449, and is completed., Findings: Between June 27 and Sept 30, 2021, 1394 participants of the 1741 screened were randomly assigned to AZD1222 or AZD2816 following an AZD1222 (n=373, n=377) or mRNA vaccine (n=322, n=322) primary series. In SARS-CoV-2-seronegative participants receiving AZD1222 or AZD2816, 78% and 80% (AZD1222 primary series) and 90% and 93%, respectively (mRNA vaccine primary series) reported solicited adverse events to the end of day 8; 2%, 2%, 1%, and 1% had serious adverse events and 12%, 12%, 10%, and 11% had adverse events of special interest, respectively, to the end of day 180. The primary immunogenicity non-inferiority endpoint was met: day-29 neutralising antibody GMT ratios (ancestral SARS-CoV-2) were 1·02 (95% CI 0·90-1·14) and 3·47 (3·09-3·89) with AZD1222 booster versus historical controls (AZD1222 and mRNA vaccine primary series, respectively). Responses against beta were greater with AZD2816 versus AZD1222 (GMT ratios, AZD1222, mRNA vaccine primary series 1·84 [1·63-2·08], 2·22 [1·99-2·47])., Interpretation: Both boosters were well tolerated, with immunogenicity against ancestral SARS-CoV-2 similar to AZD1222 primary-series vaccination. AZD2816 gave greater immune responses against beta versus AZD1222., Funding: AstraZeneca., Competing Interests: Declaration of interests MNR declares institutional support for the study from AstraZeneca. EJK, SS, AC, MK, GTT, JV, PAS, MNP, TV, NM-A, and JAG are, or were, employees of and may hold (or have held) stock or stock options in AstraZeneca. PID declares institutional support for the study from AstraZeneca, and institutional grants from AstraZeneca, Janssen, Moderna, and Atea. RP declares institutional support for the study from AstraZeneca. MA declares support for the study from AstraZeneca and IQVIA to the Clinical Infection Research Group. PKA declares institutional grants to support the conduct of the study from AstraZeneca and the UK Vaccine Taskforce via National Institute for Health Research (NIHR). BJ is an employee of Cytel and is currently on assignment to AstraZeneca. SM is an employee of Exploristics and is currently on assignment to AstraZeneca. TL reports consulting fees from Vaccitech on an unrelated project, an honorarium from Seqirus, grant support from the Vaccine Taskforce for this trial, work-related investments, and is named as an inventor on a patent application for a vaccine against SARS-CoV-2. AJP was a member of WHO's Strategic Advisory Group of Experts on Immunization until January, 2022 and remains chair of the UK Department of Health and Social Care's Joint Committee on Vaccination and Immunisation (JCVI) but does not participate in the JCVI COVID-19 committee; and reports providing advice to Shionogi on COVID-19, and funding from the NIHR, AstraZeneca, the Bill & Melinda Gates Foundation, Wellcome, the Medical Research Council, and the Coalition for Epidemic Preparedness Innovations. Oxford University has entered into a partnership with AstraZeneca for the development of COVID-19 vaccines. VL and SB declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Patients with eosinophilic severe asthma (SA) have an increased risk of asthma exacerbations. Benralizumab is approved for eosinophilic SA, and there is great value in understanding real-world effectiveness., Objective: The aim of this analysis was to examine the effectiveness of benralizumab in a real-world cohort of subspecialist-treated US patients with eosinophilic SA., Methods: CHRONICLE is an ongoing, noninterventional study of subspecialist-treated US adults with SA receiving biologics, maintenance systemic corticosteroids, or those persistently uncontrolled by high-dose inhaled corticosteroids with additional controllers. For this analysis, eligible patients enrolled from February 2018 to February 2021, had received ≥ 1 dose of benralizumab, and had study data for ≥ 3 months before and after benralizumab initiation. The primary analysis included patients with prior exacerbations reported and 12 months of outcomes data before and after initiation. Patient outcomes occurring 6-12 months before and after initiation were also evaluated., Results: A total of 317 patients had ≥ 3 months of follow-up before and after first benralizumab dose. For patients with 12 months (n = 107) and 6-12 months (n = 166) of data, significant reductions were observed in annualized rates of exacerbations (62%; P < 0.001 and 65%; P < 0.001, respectively), with similar reductions in the rates of hospitalizations and emergency department visits. Benralizumab recipients with blood eosinophil counts (BEC) of ≥ 300/ μL and < 300/ μL at baseline and 12 months of data also had significant reductions in exacerbations (68%; P < 0.001, 61%; P < 0.001)., Conclusion: This real-world, noninterventional analysis reinforces the clinical value of benralizumab in the management of patients with eosinophilic SA., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests RA Panettieri Jr.: Advisory boards and grant support — AstraZeneca, Sanofi, Genentech, Regeneron, Novartis. N Lugogo: Received consulting fees — Amgen, AstraZeneca, Avillion, Genentech, GlaxoSmithKline, Novartis, Regeneron, Sanofi, and Teva; honoraria for non-speakers bureau presentations — GlaxoSmithKline and AstraZeneca; travel support — Astra Zeneca; her institution received research support — Amgen, AstraZeneca, Avillion, Evidera, Gossamer Bio, Genentech, GlaxoSmithKline, Regeneron, Sanofi, Novartis and Teva; honorary faculty member — Observational and Pragmatic Research Institute (OPRI) but does not receive compensation for this role. WC Moore: Advisory boards — AstraZeneca, Sanofi, Genentech, GlaxoSmithKline, Regeneron. BE Chipps: Advisory boards, consultant, and speaker — AstraZeneca, Boehringer Ingelheim, Genentech, Novartis, Regeneron, Sanofi Genzyme. B Jepson: Employee — Cytel, on assignment to AstraZeneca. W Zhou: Employee — ClinChoice. CS Ambrose: Employee and shareholder — AstraZeneca. E Genofre: at the time of this study, was an employee and shareholder — AstraZeneca. D Carstens: Employee and shareholder — AstraZeneca., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Taxol is an antitumor drug derived from the bark of the Pacific Yew tree that inhibits microtubule disassembly, resulting in cell cycle arrest in late G2 and M phases. Additionally, Taxol increases cellular oxidative stress by generating reactive oxygen species. We hypothesized that the inhibition of specific DNA repair machinery/mechanisms would increase cellular sensitivity to the oxidative stress capacity of Taxol. Initial screening using Chinese hamster ovary (CHO) cell lines demonstrated that base excision repair deficiency, especially PARP deficiency, caused cellular Taxol hypersensitivity. Taxane diterpenes-containing Taxus yunnanensis extract also showed hypertoxicity in PARP deficient cells, which was consistent with other microtubule inhibitors like colcemid, vinblastine, and vincristine. Acute exposure of 50 nM Taxol treatment induced both significant cytotoxicity and M-phase arrest in PARP deficient cells, but caused neither significant cytotoxicity nor late G2-M cell cycle arrest in wild type cells. Acute exposure of 50 nM Taxol treatment induced oxidative stress and DNA damage. The antioxidant Ascorbic acid 2 glucoside partially reduced the cytotoxicity of Taxol in PARP deficient cell lines. Finally, the PARP inhibitor Olaparib increased cytotoxicity of Taxol in wild type CHO cells and two human cancer cell lines. Our study clearly demonstrates that cytotoxicity of Taxol would be enhanced by inhibiting PARP function as an enzyme implicated in DNA repair for oxidative stress., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in coronavirus disease 2019 (COVID-19) vaccinees typically produces milder disease than infection in unvaccinated individuals., Methods: To explore disease attenuation, we examined COVID-19 symptom burden and immuno-virologic responses to symptomatic SARS-CoV-2 infection in participants (AZD1222: n=177/17,617; placebo: n=203/8,528) from a 2:1 randomized, placebo-controlled, phase 3 study of two-dose primary series AZD1222 (ChAdOx1 nCoV-19) vaccination (NCT04516746)., Results: We observed that AZD1222 vaccinees had an overall lower incidence and shorter duration of COVID-19 symptoms compared with placebo recipients, as well as lower SARS-CoV-2 viral loads and a shorter median duration of viral shedding in saliva. Vaccinees demonstrated a robust antibody recall response versus placebo recipients with low-to-moderate inverse correlations with virologic endpoints. Vaccinees also demonstrated an enriched polyfunctional spike-specific Th-1-biased CD4+ and CD8+ T-cell response that was associated with strong inverse correlations with virologic endpoints., Conclusion: Robust immune responses following AZD1222 vaccination attenuate COVID-19 disease severity and restrict SARS-CoV-2 transmission potential by reducing viral loads and the duration of viral shedding in saliva. Collectively, these analyses underscore the essential role of vaccination in mitigating the COVID-19 pandemic., Competing Interests: JM, BA, AAA, TE, KS, AMS, MP, PAS, DW, TV, JAG, and EJK are current employees of AstraZeneca and hold or may hold AstraZeneca stock. HB and NP are contractors to AstraZeneca via Bogier consulting. BJ is a contractor to AstraZeneca via Cytel. SS is a contractor to AstraZeneca via Joule/System One. ARF has received institutional grants for research from Pfizer, Merck, Sharpe and Dohme, Janssen, and BioFire Diagnostics and has received fees for serving on Novavax COVID-19 vaccine Data and Safety Monitoring Board. MES declares grants from the NIH and NIAID during the conduct of the study and institutional research grants from the Bill and Melinda Gates Foundation, Gilead Sciences, Janssen Global Services, LLC, Merck, and Sanofi Pasteur Inc. AFL has received institutional research grants from AstraZeneca and Gilead Sciences. GCP has received institutional research grants from AstraZeneca, Pfizer, and Moderna. SAR has received institutional grants from the NIH and NIAID from clinical trial enrolment and provides pro bono consultancy to Novimmune for novimab. MLR declares funding for consultancy from the Walter Reed Army Institute of Research and for serving on their behalf in Operation Warp Speed. C-PR has received institutional research grants from Gilead Sciences and ViiV Healthcare, honoraria for lectures from Gilead Sciences, ViiV Healthcare and Vindico CME, and sits on advisory boards for Janssen, Gilead Sciences, and ViiV Healthcare. BES has received research funding from the US government under the COVID-19 Prevention Network initiative, institutional research grants from Gilead Sciences, ViiV Healthcare, and the University of Chicago and payment or honoraria from MATEC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. This study received funding from AstraZeneca. The funder had the following involvement with the study with input from the external authors: study design; collection, analysis and interpretation of data; the writing of this article and the decision to submit it for publication. The first draft of the manuscript was written under the direction of the authors by a medical writer funded by AstraZeneca., (Copyright © 2023 Maaske, Sproule, Falsey, Sobieszczyk, Luetkemeyer, Paulsen, Riddler, Robb, Rolle, Sha, Tong, Ahani, Aksyuk, Bansal, Egan, Jepson, Padilla, Patel, Shoemaker, Stanley, Swanson, Wilkins, Villafana, Green and Kelly.)

Introduction: Atropine sulfate is an FDA-approved medical countermeasure (MCM) for the treatment of organophosphorus nerve agent and organophosphate pesticide toxicity. Sufficient MCM supplies must be available in an incident involving a mass human exposure either from an accidental chemical release or a terrorist attack., Methods: We performed a randomized, 3-sequence, 3-period phase I crossover study to assess the bioavailability and pharmacokinetics (PK) of a single dose (0.5 mg and 1.0 mg) of 1% ophthalmic atropine sulfate solution administered sublingually to 15 healthy adult volunteers. The primary endpoint was evaluation of the bioavailability of each of the two sublingual doses against a 1.0 mg reference intravenous (IV) atropine dose. Secondary endpoints included the safety and tolerability (xerostomia scale) of atropine sulfate administered sublingually., Results: Sublingual atropine was safe (no severe AEs or SAEs were reported with either dose) and well tolerated, with a single subject reaching maximum xerostomia on a single dosing day. The geometric mean AUC ∞ was 286.40, 493.81, and 816.47 min*ng/mL for the 0.5 mg and 1.0 mg sublingual doses, and the 1.0 mg IV dose, respectively. Compared to IV administration, the 1.0 mg sublingual dose produced 0.60 (90% CI: 0.55-0.66) of the overall concentration of atropine over time (AUC ∞ )., Conclusion: Sublingual atropine sulfate 1% ophthalmic solution may be an alternative formulation and route of administration combination which expands the capacity and dosing options of atropine as a nerve agent MCM., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Objective: To identify, summarise and evaluate evidence on the correlation between perceived and actual neighbourhood safety (personal and road danger) and diverse forms of outdoor active mobility behaviour (ie, active play, exercise, and travel) among primary-school-aged children., Design: A systematic review of evidence from observational studies exploring children's active mobility behaviour and safety., Data Sources: Six electronic databases were searched: Google Scholar, PubMed, Scopus, Science Direct, ProQuest and Web of Science from study inception until July 2020., Data Extraction and Synthesis: Study selection and quality assessment were conducted independently by two reviewers. We expanded on a quality assessment tool and adopted a vote-counting technique to determine strength of evidence. The outcomes were categorised by individual, family and neighbourhood levels., Results: A total of 29 studies were included, with a majority of cross-sectional design. Higher parental perceived personal safety correlated with increased children's active mobility behaviour, but most commonly in active travel (eg, independent walking or cycling to a local destination). Increased concerns regarding road danger correlated with a decrease in each type of children's active behaviour; active travel, play and exercise. However, these correlations were influenced by child's sex/gender, age, car ownership, neighbourhood types, across time, and proximity to destination. Limited or inconclusive evidence was found on correlate of children's outdoor active mobility behaviour to 'stranger danger', children's perceived personal safety, race/ethnicity, socioeconomic status or measured safety., Conclusion: Children are restricted by perception of safety. Encouraging children's active travel may require future strategies to address characteristics relevant to types of the neighbourhood that promote a high sense of personal safety. Children and parents may embrace other types of active mobility behaviour if road danger is mitigated. Sex/gender and age-specific interventions and redesign of public places could lead to child-friendly cities. Future studies may benefit from adopting validated measurement methods and fill existing research gaps., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Staphylococcus aureus colonizes patients with atopic dermatitis (AD) and exacerbates disease by promoting inflammation. The present study investigated the safety and mechanisms of action of Staphylococcus hominis A9 (ShA9), a bacterium isolated from healthy human skin, as a topical therapy for AD. ShA9 killed S. aureus on the skin of mice and inhibited expression of a toxin from S. aureus (psmα) that promotes inflammation. A first-in-human, phase 1, double-blinded, randomized 1-week trial of topical ShA9 or vehicle on the forearm skin of 54 adults with S. aureus-positive AD (NCT03151148) met its primary endpoint of safety, and participants receiving ShA9 had fewer adverse events associated with AD. Eczema severity was not significantly different when evaluated in all participants treated with ShA9 but a significant decrease in S. aureus and increased ShA9 DNA were seen and met secondary endpoints. Some S. aureus strains on participants were not directly killed by ShA9, but expression of mRNA for psmα was inhibited in all strains. Improvement in local eczema severity was suggested by post-hoc analysis of participants with S. aureus directly killed by ShA9. These observations demonstrate the safety and potential benefits of bacteriotherapy for AD.