tbuckley/cabot-search huggingface dataset:
HTLV-1 infection promotes excessive T cell activation and transformation into adult T cell leukemia/lymphoma
Authors: Benjy J.Y. Tan, Kenji Sugata, Omnia Reda, Misaki Matsuo, Kyosuke Uchiyama, Paola Miyazato, Vincent Hahaut, Makoto Yamagishi, Kaoru Uchimaru, Yutaka Suzuki, Takamasa Ueno, Hitoshi Suzushima, Hiroo Katsuya, Masahito Tokunaga, Yoshikazu Uchiyama, Hideaki Nakamura, Eisaburo Sueoka, Atae Utsunomiya, Masahiro Ono, Yorifumi Satou
Journal: Journal of Clinical Investigation (2021)

Human T cell leukemia virus type 1 (HTLV-1) mainly infects CD4+ T cells and induces chronic, persistent infection in infected individuals, with some developing adult T cell leukemia/lymphoma (ATL). HTLV-1 alters cellular differentiation, activation, and survival; however, it is unknown whether and how these changes contribute to the malignant transformation of infected cells. In this study, we used single-cell RNA-sequencing and T cell receptor-sequencing to investigate the differentiation and HTLV-1-mediated transformation of T cells. We analyzed 87,742 PBMCs from 12 infected and 3 uninfected individuals. Using multiple independent bioinformatics methods, we demonstrated the seamless transition of naive T cells into activated T cells, whereby HTLV-1-infected cells in an activated state further transformed into ATL cells, which are characterized as clonally expanded, highly activated T cells. Notably, the greater the activation state of ATL cells, the more they acquire Treg signatures. Intriguingly, the expression of HLA class II genes in HTLV-1-infected cells was uniquely induced by the viral protein Tax and further upregulated in ATL cells. Functional assays revealed that HTLV-1-infected cells upregulated HLA class II molecules and acted as tolerogenic antigen-presenting cells to induce anergy of antigen-specific T cells. In conclusion, our study revealed the in vivo mechanisms of HTLV-1-mediated transformation and immune escape at the single-cell level.
Six month immunogenicity of COVID-19 mRNA-BNT162b2 vaccine in actively treated cancer patients: updated results of the Vax-On study
Authors: F. Nelli, A. Fabbri, A. Onorato, D. Giannarelli, M.A. Silvestri, G. Pessina, J.R. Giron Berrios, A. Virtuoso, E. Marrucci, M. Schirripa, M. Mazzotta, V. Panichi, P. Cercola, C. Signorelli, M.G. Chilelli, F. Primi, E.M. Ruggeri
Journal: Annals of Oncology (2021)
MET inhibitor tepotinib antagonizes multidrug resistance mediated by ABCG2 transporter: In vitro and in vivo study
Authors: Zhuo-Xun Wu, Qiu-Xu Teng, Yuqi Yang, Nikita Acharekar, Jing-Quan Wang, Min He, Sabesan Yoganathan, Jun Lin, Jian Wang, Zhe-Sheng Chen
Journal: Acta Pharmaceutica Sinica B (2021)

Overexpression of ABCG2 transporter in cancer cells has been linked to the development of multidrug resistance (MDR), an obstacle to cancer therapy. Our recent study uncovered that the MET inhibitor, tepotinib, is a potent reversal agent for ABCB1-mediated MDR. In the present study, we reported for the first time that the MET inhibitor tepotinib can also reverse ABCG2-mediated MDR in vitro and in vivo by directly binding to the drug-binding site of ABCG2 and reversibly inhibiting ABCG2 drug efflux activity, therefore enhancing the cytotoxicity of substrate drugs in drug-resistant cancer cells. Furthermore, the ABCB1/ABCG2 double-transfected cell model and ABCG2 gene knockout cell model demonstrated that tepotinib specifically inhibits the two MDR transporters. In mice bearing drug-resistant tumors, tepotinib increased the intratumoral accumulation of ABCG2 substrate drug topotecan and enhanced its antitumor effect. Therefore, our study provides a new potential of repositioning tepotinib as an ABCG2 inhibitor and combining tepotinib with substrate drugs to antagonize ABCG2-mediated MDR.
A human orthogonal IL-2 and IL-2Rβ system enhances CAR T cell expansion and antitumor activity in a murine model of leukemia
Authors: Qian Zhang, Morgan E. Hresko, Lora K. Picton, Leon Su, Michael J. Hollander, Selene Nunez-Cruz, Zheng Zhang, Charles-Antoine Assenmacher, Jonathan T. Sockolosky, K. Christopher Garcia, Michael C. Milone
Journal: Science Translational Medicine (2021)

A human IL-2 and IL-2Rβ orthogonal cytokine-receptor pair enables a tunable approach to enhancing CAR T cell engraftment and antitumor efficacy.
Association of Social Risk Factors With Home Dialysis and Kidney Transplant Rates in Dialysis Facilities
Authors: Rebecca Thorsness, Virginia Wang, Rachel E. Patzer, Kelsey Drewry, Vincent Mor, Momotazur Rahman, Amal N. Trivedi
Journal: JAMA (2021)

This study examines rates of home dialysis and transplant at dialysis facilities that serve patients with high social risk to understand how they fare under the End-Stage Renal Disease Treatment Choices Model.
SEP-1—Taking the Measure of a Measure
Authors: Foster Gesten, Laura Evans
Journal: JAMA Network Open (2021)

Chanu Rhee, MD, MPH; Tingting Yu, PhD; Rui Wang, PhD; Sameer S. Kadri, MD, MSc; David Fram, BA; Huai-Chun Chen, PhD; Michael Klompas, MD, MPH; CDC Prevention Epicenters Program
44P Biomarker analysis from a phase Ib, multicenter, open-label clinical trial of talimogene laherparepvec (T-VEC) injected (inj) into metastatic and primary liver tumors
Authors: J.R. Hecht, M. Peeters, M. Martin Jimenez, M. Pless, A. Cubillo, J. Garcia-Corbacho, N. Mach, A. Digklia, H. Park, V. Subbiah, K. Gorski, A. Anderson, C. Liu, W. Snyder, J. Chesney
Journal: Annals of Oncology (2021)
Radiologic Imaging for High-Stage Cutaneous Squamous Cell Carcinomas
Authors: Emily S. Ruiz
Journal: JAMA Dermatology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
A small molecule targeting ALOX12-ACC1 ameliorates nonalcoholic steatohepatitis in mice and macaques
Authors: Xiao-Jing Zhang, Yan-Xiao Ji, Xu Cheng, Yanjie Cheng, Hailong Yang, Junyong Wang, Ling-Ping Zhao, Yong-Ping Huang, Dating Sun, Hui Xiang, Li-Jun Shen, Peng-Long Li, Jun-Peng Ma, Rui-Feng Tian, Juan Yang, Xinxin Yao, Haibo Xu, Rufang Liao, Li Xiao, Peng Zhang, Xin Zhang, Guang-Nian Zhao, Xi Wang, Man-Li Hu, Song Tian, Juan Wan, Jingjing Cai, Xinliang Ma, Qingbo Xu, Yibin Wang, Rhian M. Touyz, Peter P. Liu, Rohit Loomba, Zhi-Gang She, Hongliang Li
Journal: Science Translational Medicine (2021)

IMA-1 targets the ALOX12-ACC1 interaction to both prevent and treat NASH without inducing hyperlipidemia.
Methodological Standards for the Design, Implementation, and Analysis of Randomized Trials in Cardiac Surgery: A Scientific Statement From the American Heart Association
Authors: Mario Gaudino, Joanna Chikwe, Emilia Bagiella, Deepak L. Bhatt, Torsten Doenst, Stephen E. Fremes, Jennifer Lawton, Ruth M. Masterson Creber, Robert M. Sade, Brittany A. Zwischenberger
Journal: Circulation (2021)

Cardiac surgery presents specific methodological challenges in the design, implementation, and analysis of randomized controlled trials. The purposes of this scientific statement are to review key standards in cardiac surgery randomized trial design and implementation, and to provide recommendations for conducting and interpreting cardiac surgery trials. Recommendations include a careful evaluation of the suitability of the research question for a clinical trial, assessment of clinical equipoise, feasibility of enrolling a representative patient cohort, impact of practice variations on the safety and efficacy of the study intervention, likelihood and impact of crossover, and duration of follow-up. Trial interventions and study end points should be predefined, and appropriate strategies must be used to ensure adequate deliverability of the trial interventions. Every effort must be made to ensure a high completeness of follow-up; trial design and analytic techniques must be tailored to the specific research question and trial setting.
Safety of peanut (Arachis hypogaea) allergen powder-dnfp in children and teenagers with peanut allergy: Pooled summary of phase 3 and extension trials
Authors: Kari R. Brown, James Baker, Andrea Vereda, Kirsten Beyer, A. Wesley Burks, George du Toit, Jonathan O’B Hourihane, Stacie M. Jones, David Norval, Adrian Dana, Wayne Shreffler, Brian P. Vickery, Thomas Casale, Ben Skeel, Daniel Adelman
Journal: Journal of Allergy and Clinical Immunology (2021)
CD117 Antibody Drug Conjugate-Based Conditioning Allows for Efficient Engraftment of Gene-Modified CD34+ Cells in a Rhesus Gene Therapy Model
Authors: Naoya Uchida, Ulana Stasula, Malikiya Hinds, Paula Germino-Watnick, Allen E. Krouse, N Seth Linde, Aylin C. Bonifacino, Kellie Latimer, Prashant Bhattarai, Nicholas C. Yoder, Rahul Palchaudhuri, Qing Li, Kirk Bertelsen, Lisa Olson, Robert E. Donahue, John F. Tisdale
Journal: Blood (2021)
A sensitive GRAB sensor for detecting extracellular ATP in vitro and in vivo
Authors: Zhaofa Wu, Kaikai He, Yue Chen, Hongyu Li, Sunlei Pan, Bohan Li, Tingting Liu, Fengxue Xi, Fei Deng, Huan Wang, Jiulin Du, Miao Jing, Yulong Li
Journal: Neuron (2021)
CXCR4 induces podocyte injury and proteinuria by activating β-catenin signaling
Authors: Hongyan Mo, Qian Ren, Dongyan Song, Bo Xu, Dong Zhou, Xue Hong, Fan Fan Hou, Lili Zhou, Youhua Liu
Journal: Theranostics (2021)

Background: C-X-C chemokine receptor type 4 (CXCR4) plays a crucial role in mediating podocyte dysfunction, proteinuria and glomerulosclerosis.However, the underlying mechanism remains poorly understood.Here we studied the role of β-catenin in mediating CXCR4-triggered podocyte injury.Methods: Mouse models of proteinuric kidney diseases were used to assess CXCR4 and β-catenin expression.We utilized cultured podocytes and glomeruli to delineate the signal pathways involved.Conditional knockout mice with podocyte-specific deletion of CXCR4 were generated and used to corroborate a role of CXCR4/β-catenin in podocyte injury and proteinuria.Results: Both CXCR4 and β-catenin were induced and colocalized in the glomerular podocytes in several models of proteinuric kidney diseases.Activation of CXCR4 by its ligand SDF-1α stimulated β-catenin activation but did not affect the expression of Wnt ligands in vitro.Blockade of β-catenin signaling by ICG-001 preserved podocyte signature proteins and inhibited Snail1 and MMP-7 expression in vitro and ex vivo.Mechanistically, activation of CXCR4 by SDF-1α caused the formation of CXCR4/β-arrestin-1/Src signalosome in podocytes, which led to sequential phosphorylation of Src, EGFR, ERK1/2 and GSK-3β and ultimately β-catenin stabilization and activation.Silencing β-arrestin-1 abolished this cascade of events and inhibited β-catenin in response to CXCR4 stimulation.Podocyte-specific knockout of CXCR4 in mice abolished β-catenin activation, preserved podocyte integrity, reduced proteinuria and ameliorated glomerulosclerosis after Adriamycin injury.Conclusion: These results suggest that CXCR4 promotes podocyte dysfunction and proteinuria by assembling CXCR4/β-arrestin-1/Src signalosome, which triggers a cascade of signal events leading to β-catenin activation.
Functional impairment of CD19 <sup>+</sup> CD24 <sup>hi</sup> CD38 <sup>hi</sup> B cells in neuromyelitis optica spectrum disorder is restored by B cell depletion therapy
Authors: Yeseul Kim, So Yeon Kim, Sang-Min Han, Rosah May Payumo, Kevin Park, Ha Eun Kim, Su-Hyun Kim, Jae-Won Hyun, Eunjig Lee, Ho Jin Kim
Journal: Science Translational Medicine (2021)

Defective regulatory B cells that contribute to autoimmunity are recovered by B cell depletion therapy in patients with NMOSD.
Guidance for the implementation of a safety checklist for gastrointestinal endoscopic procedures: European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) Position Statement
Authors: Ian M. Gralnek, Raf Bisschops, Manmeet Matharoo, Matthew Rutter, Andrew Veitch, Peter Meier, Ulrike Beilenhoff, Cesare Hassan, Mario Dinis-Ribeiro, Helmut Messmann
Journal: Endoscopy (2021)

SOURCE AND SCOPE This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It provides guidance on the collection and handling of tissue samples during endoscopy of the lower gastrointestinal tract. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence.
Abstract 13048: A Simple Model to Describe the Relationship Between Compression Force and Depth During CPR
Authors: Jose Julio Gutiérrez, CAMILO L SANDOVAL, Mikel Leturiondo, Koldo Redondo, James K Russell, Mohamud R Daya, Sofia Ruiz De Gauna
Journal: Circulation (2021)

Aim: The relationship between force and depth during manual chest compressions depends on the patient and on the dynamics with which the rescuer applies the force. Force-depth models with many fitting parameters have been proposed making physical interpretation complicated. The aim of this work was to design a simpler force-depth model, accommodating anticipated differences in compression and recoil phases. Materials and Methods: Force and acceleration signals were extracted from out-of-hospital-cardiac arrest (OHCA) defibrillator recordings (TVF&amp;R, OR, USA), equipped with CPR technology. Compression depth and velocity signals were computed from acceleration. We analyzed intervals of 20-s within the 1st min of chest compressions. Our model decomposes the applied force as the sum of an elastic and a damped term, considering different damping coefficients for the compression and recoil phases. Coefficient of elasticity was calculated at the instant of maximum compression depth (null velocity) and damping coefficients at the instants of maximum compression and recoil velocities. The estimated depth signal is shown in the figure. The goodness of the model was assessed through the determination coefficient R 2 . Results: We analyzed 1,074 compressions from 30 OHCA recordings. Median (IQR) compression depth was 4.6 (4.0-5.4) cm; compression rate was 107 (102–113) cpm; coefficient of elasticity was 100.67 (78.95–125.01) N/cm; compression damping coefficient was 2.57 (1.84–3.29) N/(cm/s) and recoil damping coefficient was 3.59 (2.58–4.90) N/(cm/s). Median R 2 was 0.993 (0.984–0.996). Conclusions: This model, derived using fewer parameters, could help with the interpretation of the mechanical properties of the chest during CPR. It may also be useful for the assessment of inter-patient differences with age, sex, and body constitution, as well as of the evolution of elasticity and damping of patient’s chest during the course of resuscitation.
Rapid Phospholipid Turnover after Surfactant Nebulization in Severe COVID-19 Infection: A Randomized Clinical Trial
Authors: Anthony D. Postle, Howard W. Clark, Jim Fink, Jens Madsen, Grielof Koster, Madhuriben Panchal, Ratko Djukanovic, David Brealey, Michael P. W. Grocott, Ahilanandan Dushianthan
Journal: American Journal of Respiratory and Critical Care Medicine (2021)
The Next Frontier of Less Is More—From Description to Implementation
Authors: Niloofar Latifi, Rita F. Redberg, Deborah Grady
Journal: JAMA Internal Medicine (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Multidisciplinary Provider Insights to Promote Adoption of Bispecific Antibodies to Treat Cancer in the Community
Authors: Limaya Atembina, Leigh Boehmer, Kelly Terrell, Rima Koka, Murali Janakiram, Axel Grothey, Amy L Morris, Srinivas Devarakonda, Barbara Rogers, Ronan Kelly, Jesus Berdeja, Firas El Chaer
Journal: Blood (2021)
Genomic and transcriptomic characterization of heterogeneous immune subgroups of microsatellite instability-high colorectal cancers
Authors: Jung Ho Kim, Mi-Kyoung Seo, Ji Ae Lee, Seung-Yeon Yoo, Hyeon Jeong Oh, Hyundeok Kang, Nam-Yun Cho, Jeong Mo Bae, Gyeong Hoon Kang, Sangwoo Kim
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Colorectal cancers (CRCs) with microsatellite instability-high (MSI-H) are hypermutated tumors and are generally regarded as immunogenic. However, their heterogeneous immune responses and underlying molecular characteristics remain largely unexplained. Methods We conducted a retrospective analysis of 73 primary MSI-H CRC tissues to characterize heterogeneous immune subgroups. Based on combined tumor-infiltrating lymphocyte (TIL) immunoscore and tertiary lymphoid structure (TLS) activity, MSI-H CRCs were classified into immune-high, immune-intermediate, and immune-low subgroups. Of these, the immune-high and immune-low subgroups were further analyzed using whole-exome and transcriptome sequencing. Results We found considerable variations in immune parameters between MSI-H CRCs, and immune subgrouping of MSI-H CRCs was performed accordingly. The TIL densities and TLS activities of immune-low MSI-H CRCs were comparable to those of an immune-low or immune-intermediate subgroup of microsatellite-stable CRCs. There were remarkable differences between immune-high and immune-low MSI-H CRCs, including their pathological features (medullary vs mucinous), genomic alterations (tyrosine kinase fusions vs KRAS mutations), and activated signaling pathways (immune-related vs Wnt and Notch signaling), whereas no significant differences were found in tumor mutational burden (TMB) and neoantigen load. The immune-low MSI-H CRCs were subdivided by the consensus molecular subtype (CMS1 vs CMS3) with different gene expression signatures (mesenchymal/stem-like vs epithelial/goblet-like), suggesting distinct immune evasion mechanisms. Angiogenesis and CD200 were identified as potential therapeutic targets in immune-low CMS1 and CMS3 MSI-H CRCs, respectively. Conclusions MSI-H CRCs are immunologically heterogeneous, regardless of TMB. The unusual immune-low MSI-H CRCs are characterized by mucinous histology, KRAS mutations, and Wnt/Notch activation, and can be further divided into distinct gene expression subtypes, including CMS4-like CMS1 and CMS3. Our data provide novel insights into precise immunotherapeutic strategies for subtypes of MSI-H tumors.
Corrigendum to ‘First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis’
Authors: L.A. Emens, S. Adams, C.H. Barrios, V. Diéras, H. Iwata, S. Loi, H.S. Rugo, A. Schneeweiss, E.P. Winer, S. Patel, V. Henschel, A. Swat, M. Kaul, L. Molinero, S. Patel, S.Y. Chui, P. Schmid
Journal: Annals of Oncology (2021)

The authors regret that in the original publication the figure presented in Supplementary Material as Fig. S3 contained a labelling error. In the original figure should "ITT" read "PD-L1 IC+". The figure has now been corrected and replaced online. The authors would like to apologise for any inconvenience caused. First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysisAnnals of OncologyVol. 32Issue 8PreviewGuidelines recommend atezolizumab plus nab-paclitaxel (A + nP) for first-line treatment of unresectable, locally advanced, or metastatic triple-negative breast cancer expressing programmed death-ligand 1 (PD-L1) on tumor-infiltrating immune cells (IC), based on IMpassion130. We report the final overall survival (OS) and safety of that study as per the prespecified analysis plan. Full-Text PDF Open Access
Effectiveness of mRNA-1273 against delta, mu, and other emerging variants of SARS-CoV-2: test negative case-control study
Authors: Katia J Bruxvoort, Lina S Sy, Lei Qian, Bradley K Ackerson, Yi Luo, Gina S Lee, Yun Tian, Ana Florea, Michael Aragones, Julia E Tubert, Harpreet S Takhar, Jennifer H Ku, Yamuna D Paila, Carla A Talarico, Hung Fu Tseng
Journal: BMJ (2021)

To evaluate the effectiveness of the mRNA-1273 vaccine against SARS-CoV-2 variants and assess its effectiveness against the delta variant by time since vaccination.Test negative case-control study.Kaiser Permanente Southern California (KPSC), an integrated healthcare system.Adult KPSC members with a SARS-CoV-2 positive test sent for whole genome sequencing or a negative test from 1 March 2021 to 27 July 2021.Two dose or one dose vaccination with mRNA-1273 (Moderna covid-19 vaccine) ≥14 days before specimen collection versus no covid-19 vaccination.Outcomes included infection with SARS-CoV-2 and hospital admission with covid-19. In pre-specified analyses for each variant type, test positive cases were matched 1:5 to test negative controls on age, sex, race/ethnicity, and specimen collection date. Conditional logistic regression was used to compare odds of vaccination among cases versus controls, with adjustment for confounders. Vaccine effectiveness was calculated as (1-odds ratio)×100%.The study included 8153 cases and their matched controls. Two dose vaccine effectiveness was 86.7% (95% confidence interval 84.3% to 88.7%) against infection with the delta variant, 98.4% (96.9% to 99.1%) against alpha, 90.4% (73.9% to 96.5%) against mu, 96-98% against other identified variants, and 79.9% (76.9% to 82.5%) against unidentified variants (that is, specimens that failed sequencing). Vaccine effectiveness against hospital admission with the delta variant was 97.5% (92.7% to 99.2%). Vaccine effectiveness against infection with the delta variant declined from 94.1% (90.5% to 96.3%) 14-60 days after vaccination to 80.0% (70.2% to 86.6%) 151-180 days after vaccination. Waning was less pronounced for non-delta variants. Vaccine effectiveness against delta infection was lower among people aged ≥65 years (75.2%, 59.6% to 84.8%) than those aged 18-64 years (87.9%, 85.5% to 89.9%). One dose vaccine effectiveness was 77.0% (60.7% to 86.5%) against infection with delta.Two doses of mRNA-1273 were highly effective against all SARS-CoV-2 variants, especially against hospital admission with covid-19. However, vaccine effectiveness against infection with the delta variant moderately declined with increasing time since vaccination.