tbuckley/cabot-search huggingface dataset:
Neoadjuvant Chemotherapy and Immunotherapy in Luminal B-like Breast Cancer: Results of the Phase II GIADA Trial
Authors: Maria Vittoria Dieci, Valentina Guarneri, Anna Tosi, Giancarlo Bisagni, Antonino Musolino, Simon Spazzapan, Gabriella Moretti, Grazia Maria Vernaci, Gaia Griguolo, Tommaso Giarratano, Loredana Urso, Francesca Schiavi, Claudia Pinato, Giovanna Magni, Marcello Lo Mele, Gian Luca De Salvo, Antonio Rosato, Pierfranco Conte
Journal: Clinical Cancer Research (2021)

Abstract Purpose: The role of immunotherapy in hormone receptor (HR)-positive, HER2-negative breast cancer is underexplored. Patients and Methods: The neoadjuvant phase II GIADA trial (NCT04659551, EUDRACT 2016-004665-10) enrolled stage II–IIIA premenopausal patients with Luminal B (LumB)-like breast cancer (HR-positive/HER2-negative, Ki67 ≥ 20%, and/or histologic grade 3). Patients received: three 21-day cycles of epirubicin/cyclophosphamide followed by eight 14-day cycles of nivolumab, triptorelin started concomitantly to chemotherapy, and exemestane started concomitantly to nivolumab. Primary endpoint was pathologic complete response (pCR; ypT0/is, ypN0). Results: A pCR was achieved by 7/43 patients [16.3%; 95% confidence interval (CI), 7.4–34.9]; the rate of residual cancer burden class 0–I was 25.6%. pCR rate was significantly higher for patients with PAM50 Basal breast cancer (4/8, 50%) as compared with other subtypes (LumA 9.1%; LumB 8.3%; P = 0.017). Tumor-infiltrating lymphocytes (TIL), immune-related gene-expression signatures, and specific immune cell subpopulations by multiplex immunofluorescence were significantly associated with pCR. A combined score of Basal subtype and TILs had an AUC of 0.95 (95% CI, 0.89–1.00) for pCR prediction. According to multiplex immunofluorescence, a switch to a more immune-activated tumor microenvironment occurred following exposure to anthracyclines. Most common grade ≥3 treatment-related adverse events (AE) during nivolumab were γ-glutamyltransferase (16.7%), alanine aminotransferase (16.7%), and aspartate aminotransferase (9.5%) increase. Most common immune-related AEs were endocrinopathies (all grades 1–2; including adrenal insufficiency, n = 1). Conclusions: Luminal B-like breast cancers with a Basal molecular subtype and/or a state of immune activation may respond to sequential anthracyclines and anti–PD-1. Our data generate hypotheses that, if validated, could guide immunotherapy development in this context.
Effectiveness of local anesthetic application methods in postoperative pain control in laparoscopic cholecystectomies; a randomised controlled trial
Authors: Anil Ergin, Mehmet Timuçin Aydin, Hüseyin Çiyiltepe, Aziz Bora Karip, Mehmet Mahir Fersahoğlu, Yetkin Özcabi, Birol Ağca, Ahmet Yalin İşcan, Yasin Güneş, Arzu Yildirim Ar, İksan Taşdelen, Kemal Memişoğlu
Journal: International Journal of Surgery (2021)
Circadian clocks guide dendritic cells into skin lymphatics
Authors: Stephan J. Holtkamp, Louise M. Ince, Coline Barnoud, Madeleine T. Schmitt, Flore Sinturel, Violetta Pilorz, Robert Pick, Stéphane Jemelin, Michael Mühlstädt, Wolf-Henning Boehncke, Jasmin Weber, David Laubender, Julia Philippou-Massier, Chien-Sin Chen, Leonie Holtermann, Dietmar Vestweber, Markus Sperandio, Barbara U. Schraml, Cornelia Halin, Charna Dibner, Henrik Oster, Jörg Renkawitz, Christoph Scheiermann
Journal: Nature Immunology (2021)

Abstract Migration of leukocytes from the skin to lymph nodes (LNs) via afferent lymphatic vessels (LVs) is pivotal for adaptive immune responses 1,2 . Circadian rhythms have emerged as important regulators of leukocyte trafficking to LNs via the blood 3,4 . Here, we demonstrate that dendritic cells (DCs) have a circadian migration pattern into LVs, which peaks during the rest phase in mice. This migration pattern is determined by rhythmic gradients in the expression of the chemokine CCL21 and of adhesion molecules in both mice and humans. Chronopharmacological targeting of the involved factors abrogates circadian migration of DCs. We identify cell-intrinsic circadian oscillations in skin lymphatic endothelial cells (LECs) and DCs that cogovern these rhythms, as their genetic disruption in either cell type ablates circadian trafficking. These observations indicate that circadian clocks control the infiltration of DCs into skin lymphatics, a process that is essential for many adaptive immune responses and relevant for vaccination and immunotherapies.
P47.16 Preliminary Efficacy and Safety Results About a Phase II Trial of Afatinib and Bevacizumab in Untreated NSCLC Harboring EGFR Sensitive Mutations
Authors: Y. Feng, M. Zhuo, J. Zhao, H. Zhang, H. Qin, Q. Shi, Y. Huang, Y. Liu, X. Hu
Journal: Journal of Thoracic Oncology (2021)
Upregulation of type 1 conventional dendritic cells implicates antigen cross-presentation in multisystem inflammatory syndrome
Authors: Janice J. Huang, Samantha B. Gaines, Mateo L. Amezcua, Tamar R. Lubell, Peter S. Dayan, Marissa Dale, Alexis D. Boneparth, Mark D. Hicar, Robert Winchester, Mark Gorelik
Journal: Journal of Allergy and Clinical Immunology (2021)
P60.14 A United States Study Focused on Patients’ Understanding of, Attitudes Towards, and Barriers to the Use of Biomarker Testing for NSCLC
Authors: U. Roy, N. Martin, J. Schrag, L. Shivakumar, K. Gallagher, L. Dropkin, M. Molina, L. Redway, L. Boehmer
Journal: Journal of Thoracic Oncology (2021)
SARS-CoV-2 vaccine breakthrough infection following a previous infection in a healthcare worker
Authors: Aayush Gupta, Rahul Bhoyar, Shahzad Mirza, Bani Jolly, Vigneshwar Senthivel, Afra Shamnath, Mohit Kumar Divakar, Mohamed Imran, Vishu Gupta, Srashti Jyoti Agrawal, Sahjid Mukhida, Sridhar Sivasubbu, Vinod Scaria
Journal: Journal of Infection (2021)

Highlights•Symptomatic SARS-CoV-2 infection post natural infection and 2 doses of ChAdOx1.•Moderate levels of antibodies were detected 2 weeks post natural infection.•Patient tested SARS-CoV-2 positive 30 days after the second dose of vaccine.•Genomic analysis confirmed the infection with B.1.617.2 variant of SARS-CoV-2.
Cas12a variants designed for lower genome-wide off-target effect through stringent PAM recognition
Authors: Jin Zhou, Peng Chen, Hongjian Wang, Huan Liu, Yongzheng Li, Youpeng Zhang, Yankang Wu, Chonil Paek, Zaiqiao Sun, Jun Lei, Lei Yin
Journal: Molecular Therapy (2021)

Cas12a is an RNA-guided endonuclease that has been widely used for convenient multiplex gene editing with low off-target effects. To minimize off-targeting in gene editing, we engineered a variant of LbCas12a (termed Lb-K538R) with more stringent PAM recognition, lower off-targeting capability, and similar editing efficiency in vivo compared with LbCas12a. We also demonstrated that Lb2Cas12a from Lachnospiraceae bacterium MA2020 has extensive gene-editing activities in mammalian cells. Similar to Lb-K538R, the designed Lb2Cas12a variant (termed Lb2-K518R) not only had a more stringent PAM sequence change from YYN to TYN (Y is T or C, N is A, T, C, or G), but also displayed lower off-target effects, thereby enabling more potential target site selections with low off-targeting than the common TTTV (V is A, G, or C) PAM. To determine whether this type of mutation at the homologous position had similar effects in other Cas12a, As-K548R was evaluated. Based on the results of the genome-wide off-target test, As-K548R displayed lower off-target effects. Collectively, our findings indicate that the Cas proteins could be designed to be stringent in PAM recognition to reduce their off-target effects, which suggests a promising and practical approach for minimizing off-targets effects in genome editing. Cas12a is an RNA-guided endonuclease that has been widely used for convenient multiplex gene editing with low off-target effects. To minimize off-targeting in gene editing, we engineered a variant of LbCas12a (termed Lb-K538R) with more stringent PAM recognition, lower off-targeting capability, and similar editing efficiency in vivo compared with LbCas12a. We also demonstrated that Lb2Cas12a from Lachnospiraceae bacterium MA2020 has extensive gene-editing activities in mammalian cells. Similar to Lb-K538R, the designed Lb2Cas12a variant (termed Lb2-K518R) not only had a more stringent PAM sequence change from YYN to TYN (Y is T or C, N is A, T, C, or G), but also displayed lower off-target effects, thereby enabling more potential target site selections with low off-targeting than the common TTTV (V is A, G, or C) PAM. To determine whether this type of mutation at the homologous position had similar effects in other Cas12a, As-K548R was evaluated. Based on the results of the genome-wide off-target test, As-K548R displayed lower off-target effects. Collectively, our findings indicate that the Cas proteins could be designed to be stringent in PAM recognition to reduce their off-target effects, which suggests a promising and practical approach for minimizing off-targets effects in genome editing.
Abstract 13933: Clinical Outcomes of Children With Rheumatic Heart Disease: A Retrospective Registry-Based Study in Uganda
Authors: Meghan Zimmerman, Samalie M Kitooleko, Emmy Okello, Craig A Sable, Andrea Z beaton, Chris Longenecker, Peter Lwabi
Journal: Circulation (2019)

Background: Rheumatic heart disease (RHD) continues to affect children and young adults at very high rates, and disproportionately in low-resource regions of the world. Rates of disease in Uganda a...
Brain-Protective Mechanisms of Transcription Factor NRF2: Toward a Common Strategy for Neurodegenerative Diseases
Authors: Antonio Cuadrado
Journal: The Annual Review of Pharmacology and Toxicology (2021)

Neurodegenerative diseases are characterized by the loss of homeostatic functions that control redox and energy metabolism, neuroinflammation, and proteostasis. The transcription factor nuclear factor erythroid 2–related factor 2 (NRF2) is a master controller of these functions, and its overall activity is compromised during aging and in these diseases. However, NRF2 can be activated pharmacologically and is now being considered a common therapeutic target. Many gaps still exist in our knowledge of the specific role that NRF2 plays in specialized brain cell functions or how these cells respond to the hallmarks of these diseases. This review discusses the relevance of NRF2 to several hallmark features of neurodegenerative diseases and the current status of pharmacological activators that might pass through the blood-brain barrier and provide a disease-modifying effect.
循環器病の診断と治療に関するガイドライン(2005-2006年度合同研究班報告)失神の診断・治療ガイドライン
Authors: 井上博, 相澤義房, 安部治彦, 古賀義則, 小林洋一, 住友直方, 高瀬凡平, 鄭忠和, 中里祐二, 中野赳, 西崎光弘, 堀進悟, 松崎益徳, 宮武邦夫, 尾辻豊, 河野律子, 清水昭彦, 鈴木昌, 住吉正孝, 濱崎秀一, 水牧功一, 宮武論, 安田正之, 山田典一, 渡辺則和
Journal: Circulation (2007)
Inactivated vaccines may not provide adequate protection in immunosuppressed patients with rheumatic diseases
Authors: Padmanabha Shenoy, Sakir Ahmed, Aby Paul, Somy Cherian, Anuroopa Vijayan, Sageer AS Babu, Aswathy Sukumaran
Journal: Annals of the Rheumatic Diseases (2021)

Patients with autoimmune rheumatic diseases (AIRDs) are vulnerable to COVID-19 due to the presence of multiple comorbidities.1 Moreover, patients on immunosuppressants have blunted responses to vaccination as compared with healthy people.2 3 Persistence of the virus in such people may lead to the selection of more virulent mutants of SARS-CoV-2.4 It is crucial that they are prioritised for the best possible vaccine. India has crossed 650 million vaccinations with predominantly two vaccines: the adenoviral vector-borne AZD1222 (ChAdOx1 nCoV-19) and the indigenous whole-virion β-propiolactone-inactivated BBV152. In our cohort of around 1500 patients with AIRD who are being followed up to assess the immunogenicity of COVID-19 vaccines, we identified 475 patients who have completed two doses of either vaccine. Serum was collected on median 30th (range 28–35) day after the second dose of vaccine with informed consent after ethics clearance. Titres of IgG antibodies to spike protein were estimated with the Elecsys kit (Roche, Switzerland). To check the neutralisation potential of the sera, age, sex and disease matched 80 BBV152 and 85 AZD1222 recipients …
Factors Associated With Chronic De Novo Post-Coronavirus Disease Gastrointestinal Disorders in a Metropolitan US County
Authors: Christopher Vélez, Mary Paz, Casey Silvernale, Lawrence W. Stratton, Braden Kuo, Kyle Staller, Esteban Barreto, Josselyn Vergara Cobos, Kelly L. Buchanan, Taylor Boyd, Anshuman C. Desai, Shreya Chablaney, Ingrid Guerrero López, Joseph R. Betancourt
Journal: Clinical Gastroenterology and Hepatology (2021)
Deaths involving COVID-19 by self-reported disability status during the first two waves of the COVID-19 pandemic in England: a retrospective, population-based cohort study
Authors: Matthew L Bosworth, Daniel Ayoubkhani, Vahé Nafilyan, Josephine Foubert, Myer Glickman, Calum Davey, Hannah Kuper
Journal: The Lancet Public Health (2021)
Increase in invasive disease caused by Haemophilus influenzae b, the Netherlands, 2020 to 2021
Authors: Anneke Steens, Kamelia R Stanoeva, Mirjam J Knol, Rob Mariman, Hester E de Melker, Nina M van Sorge
Journal: Eurosurveillance (2021)

The incidence of most respiratory-transmitted diseases decreased during the COVID-19 pandemic as a result of containment measures. In contrast, in the Netherlands we noted an increase in invasive disease caused by Haemophilus influenzae b (Hib) (from < 0.3/100,000 before 2019 to 0.39 and 0.33/100,000 in 2020 and 2021) in vaccinated and unvaccinated age groups. We did not find a change in vaccine effectiveness against Hib invasive disease (effectiveness > 90%). We discuss factors that may have contributed to this rise.
MA08.06 Immune Cell Profiles as Predictors of Survival in Surgically Treated Non-Small Cell Lung Cancer (NSCLC)
Authors: L. Sellmer, J. Kovács, J. Neumann, J. Walter, D. Kauffmann-Guerrero, Z. Syunyaeva, J. Fertmann, C. Schneider, J. Zimmermann, J. Behr, A. Tufman
Journal: Journal of Thoracic Oncology (2021)
P06.06 Clinical Implications of Tumour Spread Through Air Spaces (STAS) In Lung Adenocarcinoma Patients Treated With Surgery
Authors: L. Gutierrez Sainz, S. Lopez Muñoz, P. Cruz Castellanos, M.I. Esteban Rodriguez, O. Higuera, J. De Castro Carpeño
Journal: Journal of Thoracic Oncology (2021)
Assessment of Changes in US Veterans Health Administration Care Delivery Methods During the COVID-19 Pandemic
Authors: Liam Rose, Linda Diem Tran, Steven M. Asch, Anita Vashi
Journal: JAMA Network Open (2021)

This cross-sectional study assesses changes in health care delivery methods, including all forms of care either purchased or provided by the Veterans Health Administration (VHA), for VHA enrollees in response to the COVID-19 pandemic.
Hydroxyurea Use After Transitions of Care Among Young Adults With Sickle Cell Disease and Tennessee Medicaid Insurance
Authors: Joacy G. Mathias, Vikki G. Nolan, Lisa M. Klesges, Sherif M. Badawy, William O. Cooper, Jane S. Hankins, Matthew P. Smeltzer
Journal: JAMA Network Open (2021)

During transition from pediatrics to adult health care, young adults with sickle cell disease (SCD) face increased risk of severe morbidities and premature mortality.1 Sickle cell disease complications can be mitigated with hydroxyurea use.2 However, successful alleviation and prevention of SCD morbidities is contingent on initiation of and continued adherence to hydroxyurea therapy.3,4 With higher frequency of SCD-related complications among young adults, we examined the prevalence of hydroxyurea prescription among patients aged 18 to 25 years using statewide claims data. Understanding the patterns of hydroxyurea use in this patient population is key to potentially preventing the high burden of the disease accumulating among young adults.
SARS-CoV-2 vaccine uptake, perspectives, and adverse reactions following vaccination in patients with cancer undergoing treatment
Authors: J.C. Figueiredo, U. Ihenacho, N.M. Merin, O. Hamid, J. Darrah, J. Gong, R. Paquette, A.C. Mita, R. Vescio, I. Mehmi, R. Basho, S.J. Salvy, C.H. Shirazipour, N. Caceres, L.J. Finster, B. Coleman, H.U. Arnow, L. Florindez, K. Sobhani, J.C. Prostko, E.C. Frias, J.L. Stewart, A. Merchant, K.L. Reckamp
Journal: Annals of Oncology (2021)
Coronary Calcium to Rule Out Obstructive Coronary Artery Disease in Patients With Acute Chest Pain
Authors: Gowtham R. Grandhi, Reed Mszar, Miguel Cainzos-Achirica, Tanuja Rajan, Muhammad A. Latif, Marcio S. Bittencourt, Leslee J. Shaw, Juan C. Batlle, Ron Blankstein, Michael J. Blaha, Ricardo C. Cury, Khurram Nasir
Journal: JACC. Cardiovascular imaging (2021)
Generation of Distal Renal Segments Involves a Unique Population of Aqp2+ Progenitor Cells
Authors: Chao Gao, Lihe Chen, Enuo Chen, Akaki Tsilosani, Yang Xia, Wenzheng Zhang
Journal: Journal of the American Society of Nephrology (2021)

Progenitor cells have clonogenicity, self-renewal, and multipotential capacity, and they can generate multiple types of cells during development. Evidence demonstrating the existence of such progenitor cells for renal distal segments is lacking.To identify Aqp2 + progenitor (AP) cells, we performed in vivo lineage tracing using both constitutive ( Aqp2Cre RFP/+ ) and Tamoxifen-inducible ( Aqp2 ECE/+ RFP/+ , Aqp2 ECE/+ Brainbow/+ , and Aqp2 ECE/+ Brainbow/Brainbow ) mouse models. Aqp2Cre RFP/+ mice were analyzed from E14.5 to adult stage. The inducible models were induced at P1 and examined at P3 and P42, respectively. Multiple segment- or cell-specific markers were used for high-resolution immunofluorescence confocal microscopy analyses to identify the cell types derived from Aqp2 + cells.Both Aqp2Cre and Aqp2 ECE/+ faithfully indicate the activation of the endogenous Aqp2 promoter for lineage tracing. A subset of Aqp2 + cells behaves as potential AP. Aqp2Cre -based lineage tracing revealed that embryonic APs generate five types of cells, which form the late distal convoluted tubule (DCT2), connecting tubule segments 1 and 2 (CNT1 and CNT2, respectively), and collecting ducts (CDs). The α - and β -intercalated cells were apparently derived from embryonic AP in a stepwise manner. Aqp2 ECE/+ -based lineage tracing identified cells coexpressing Aqp2 and V-ATPase subunits B1 and B2 as the potential AP. Neonate APs generate daughter cells either inheriting their property (self-renewal) or evolving into various DCT2, CNT, or CD cells (multipotentiality), forming single cell-derived multiple-cell clones (clonogenicity) during development.Our study demonstrates that unique Aqp2 + B1B2 + cells are the potential APs to generate DCT2, CNT, CNT2, and CD segments.
Covid-19: Government must reintroduce precautionary measures now, say health leaders
Authors: Gareth Iacobucci
Journal: BMJ (2021)

Health leaders have urged the UK government to reintroduce measures such as mandatory face coverings in crowded and enclosed spaces “without delay” to stop the NHS from being overwhelmed this winter.

Last month the government set out its “plan B for England,”1 which it will implement if data show that the NHS is likely to come under unsustainable pressure this winter. This may include introducing mandatory vaccine certification in specific settings, reintroducing the legal requirement to wear face coverings in some settings, and advising people to work from home if they can.

The UK saw 49 156 new infections on 18 October, the highest daily figure since mid-July. The number of patients in the UK being admitted to hospitals with covid has reached 900 a day—approaching the 1000 a day figure that experts …
간세포암과 만성 바이러스성 간염 환자의 간 조직 내의 Transforming Growth Factor Alpha mRNA 의 발현
Authors: 정영화(Young Hwa Chung), 김정아(Jung A Kim), 송병철(Byung Cheol Song), 이근찬(Geun Chan Lee), 고문수(Moon Soo Koh), 이영상(Young Sang Lee), 이승규(Seung Gyu Lee), 서동진(Dong Jin Suh)
Journal: Clinical and Molecular Hepatology (2000)

배경/목적 : Transforming growth factor alpha (TGFα)는 간세포의 성장에 중요한 성장인자이다. 본 연구는 만성 바이러스성 간염과 간세포암에서 TGFα) 대상과 방법: 18예의 간세포암 환자, 31예의 만성 바이러스성 간염 그리고 7예의 정상 간조직에서 TGFα mRNA의 양을 측정하였다. TGFα mRNA의 양은 역전사 중합효소연쇄반응을 이용하여 반정량하였다. 또한 만성 B형 간염 환자의 간 조직에서 HBV-RNA양은 Northern blot을 이용하여 측정하였다. 결과: 간세포암 조직에서 TGFα mRNA의 발현양은 간세포암 주위 비암성 조직 및 만성 바이러스성 간염과 정상 간 조직에 비해 의미있게 높았다. 간세포암 주위 비암성 조직의 TGFα mRNA도 만성 바이러스성 간염과 정상 간 조직에 비해 과발현되어 있었다. 또한 만성 B형 간염 조직에서 만성 C형 간염 조직에 비해 TGFα mRNA 양이 높았다. TGFα mRNA는 혈청 ALT 혹은 간 조직 내의 HBV-RNA (만성 B형 간염인 경우) 양과는 상관 관계가 없었다. 그러나, TGFα mRNA의 발현은 혈청AFP이 높은 경우 높은 경향을 보였다. 결론: 간 조직 내의 TGFα mRNA의 과발현은 간세포 괴사나 바이러스의 증식보다는 간세포의 재생능과 관련이 있을 것으로 생각된다. 또한, TGFα mRNA의 과발현은 특히 만성 B형 간염과 연관되어 간세포암의 발생 혹은 성장과 연관이 있을 것으로 생각된다. (Korean J Hepatol 2000;6:33-40)
Novel polymer-based system for intrauterine delivery of everolimus for anti-cancer applications
Authors: Brenda Melendez, Sarita Shah, Yunyun Jiang, Joseph Dottino, Emma Watson, Hannah Pearce, Mikayla Borthwick, Rosemarie E. Schmandt, Qian Zhang, Kayleah Cumpian, Joseph Celestino, Bryan Fellman, Ying Yuan, Karen H. Lu, Antonios G. Mikos, Melinda S. Yates
Journal: Journal of Controlled Release (2021)
In vivo commensal control of Clostridioides difficile virulence
Authors: Brintha P Girinathan, Nicholas DiBenedetto, Jay N Worley, Johann Peltier, Mario L Arrieta-Ortiz, Selva Rupa Christinal Immanuel, Richard Lavin, Mary L Delaney, Christopher K Cummins, Maria Hoffman, Yan Luo, Narjol Gonzalez-Escalona, Marc Allard, Andrew B Onderdonk, Georg K Gerber, Abraham L Sonenshein, Nitin S Baliga, Bruno Dupuy, Lynn Bry
Journal: Cell Host & Microbe (2021)
P24.14 Validation of Companion Diagnostics for the Identification of Patients with EGFR Exon20ins NSCLC for Amivantamab Therapy
Authors: T. Jatkoe, S. Wang, J. Odegaard, A.M. Velasco Roth, D. Osgood, G. Martinez, P. Lucas, J. Curtin, J. Karkera
Journal: Journal of Thoracic Oncology (2021)
B and T Cell Responses after a Third Dose of SARS-CoV-2 Vaccine in Kidney Transplant Recipients
Authors: Eva Schrezenmeier, Hector Rincon-Arevalo, Ana-Luisa Stefanski, Alexander Potekhin, Henriette Staub-Hohenbleicher, Mira Choi, Friederike Bachmann, Vanessa Proβ, Charlotte Hammett, Hubert Schrezenmeier, Carolin Ludwig, Bernd Jahrsdörfer, Andreia C. Lino, Kai-Uwe Eckardt, Katja Kotsch, Thomas Dörner, Klemens Budde, Arne Sattler, Fabian Halleck
Journal: Journal of the American Society of Nephrology (2021)

Accumulating evidence sugges ts solid organ transplant recipients, as opposed to the general population, show strongly impaired responsiveness toward standard SARS-CoV-2 mRNA-based vaccination, demanding alternative strategies for protectio n o f this vulnerable group.In line with recent recommendations, a third dose of either heterologous ChAdOx1 (AstraZeneca) or homologous BNT162b2 (BioNTech) was administered to 25 kidney transplant recipients (KTR) without humoral response after two doses of BNT162b2, followed by analysis of serological responses and vaccine-specific B- and T-cell immunity.Nine out of 25 (36%) KTR under standard immunosuppressive treatment seroconverted until day 27 after the third vaccination, whereas one patient developed severe COVID-19 infection immediately after vaccination. Cellular analysis 7 days after the third dose showed significantly elevated frequencies of viral spike-protein receptor-binding domain-specific B cells in humor al responders as compared with nonresponders. Likewise, portions of spike-reactive CD4 + T helper cells were significantly elevated in patients who were seroconverting. Furthermore, overall frequencies of IL-2 + , IL-4 + , and polyfunctional CD4 + T cells significantly increased after the third dose, whereas memory/effector differentiation remained unaffected.Our data suggest a fraction of transplant recipients benefit from triple vaccination, where seroconversion is associated with quantitative and qualitative changes of cellular immunity. At the same time, the study highlights that modified vaccination approaches for immunosuppressed patients remain an urgent medical need.This article contains a podcast at https://www.asn-online.org/media/podcast/JASN/2021_11_23_briggsgriffin112321.mp3.